ginsenoside-rg3 and Lung-Neoplasms

The occurrence and development of non-small cell lung cancer (NSCLC) are closely related to the immune status of the tumor-host. The immunosuppression caused by tumor cells and toxic side effects produced by chemotherapeutic drugs results in a decrease in immune function, ultimately leading to the failure of clinical chemotherapy treatment. Ginsenoside Rg3 has been clinically reported to have positive effects in enhancing immune function in patients. Thus, we screened and evaluated the quality of the evidence regarding the benefits of ginsenoside Rg3 and conducted a meta-analysis to assess the impact on improving immune function in NSCLC.. The PubMed, EMBASE, Cochrane Library, CNKI, Weipu (VIP), and Wanfang databases were searched in this study, all from the time of library construction to January 2023.. In total,12 trials with a sample size of 1008 cases were included based on the eligible criteria. The results showed that compared with first-line chemotherapy alone, the combination of ginsenoside Rg3 and first-line chemotherapy could better improve level of the CD3+ T lymphocytes [mean difference (MD) = 4.72; 95% confidence intervals (CI): 3.92, 5.53; P < .00001], CD4+ T lymphocytes (MD = 4.93; 95% CI: 4.61, 5.26; P < .00001), CD8+ T lymphocytes (MD = 2.67; 95% CI: 0.93, 4.37; P = .003), CD4+/CD8+ T lymphocytes (MD = 0.20; 95% CI: 0.09, 0.32; P = .0006), increase the activity of nature killer cells (MD = 2.11; 95% CI: 0.58, 3.63; P = .007), recover the decline of the white blood cell count induced by chemotherapy, and improve the clinical efficacy for patients.. This study confirmed that ginsenoside Rg3 has some efficacy advantages for improving immune function in patients with NSCLC.

Topics: Carcinoma, Non-Small-Cell Lung; Humans; Immunity; Lung Neoplasms; Randomized Controlled Trials as Topic

Cancer metastasis is the leading cause of death in cancer patients. Due to the limitations of conventional cancer treatment, such as chemotherapy, there is a need for novel therapeutics to prevent metastasis. Ginsenoside Rg3, a major active component of

Topics: Animals; Epithelial-Mesenchymal Transition; Ginsenosides; Lung Neoplasms; Panax

To explore the effect and mechanism of ginsenoside Rg3 (Shenyi Capsule) on the postoperative life span of patients with non-small cell lung cancer (NSCLC).. The prospective, randomized, controlled method was adopted. One hundred and thirty-three patients with NSCLC were randomly assigned to 3 groups: Shenyi Capsule group (43 cases), combined therapy group (Shenyi Capsule plus chemotherapy, 46 cases), and chemotherapy group (44 cases). The survival rates, immune function and the correlation between vascular endothelial growth factor (VEGF) expression and clinical effect were analyzed in the three groups.. (1) The 1-year survival rate in the Shenyi group, the combined group and the chemotherapy group was 76.7% (33/43), 82.6% (38/46), and 79.5% (35/44), respectively; the 2-year survival rate was 67.4% (29/43), 71.7% (33/46), and 70.5% (31/44), respectively; and the 3-year survival rate was 46.5% (20/43), 54.3% (25/46), and 47.7% (21/44), respectively. There was no significant difference among the 3 groups (P>0.05). (2) NK cells were increased to different degrees and the ratio of CD4/CD8 was normal in the Shenyi Capsule group and the combined group, while the ratio of CD4/CD8 was disproportional in the chemotherapy group. (3) In the chemotherapy group, the 3-year survival rate was lower in patients with positive expression of VEGF than in patients with negative expression (37.0% vs 64.7%, chi2=17.9, P<0.01), but no signifi cant statistical difference was shown in the other two groups (53.6% vs 55.6%, P>0.05; 44.4% vs 50.0%, P>0.05).. Shenyi Capsule, especially in combination with chemotherapy, can improve the life span of patients with NSCLC after operation. The mechanism might be correlated with improving the immune function and anti-tumor angiogenesis

Topics: Adult; Aged; Carcinoma, Non-Small-Cell Lung; Female; Ginsenosides; Humans; Lung Neoplasms; Male; Middle Aged; Prospective Studies; Survival Rate; Vascular Endothelial Growth Factor A

Lung cancer (LC) is a common cancer with high incidence and mortality rates. In recent years, ginsenoside Rg3 (Rg3), a traditional medicine, is widely used for the treatment of LC. Herein, we concentrate on assessing the effect of Rg3 on LC cell migration and invasion. The effects of Rg3 (0, 25, 50, and 100 μg/ml) on the viability, migration, invasion, angiogenesis, and expressions of epithelial-mesenchymal transition (EMT)-related proteins, cyclooxygenase-2 (COX2), and vascular endothelial growth factor (VEGF) of LC cell lines were evaluated by cell counting kit-8 (CCK-8), scratch, transwell, tube formation, and western blot assays. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to assess transfection efficiency. COX2 overexpression plasmid and short hairpin RNA for VEGF (shVEGF) were applied to evaluate whether the effect of Rg3 is related to COX2 and VEGF through rescue assay. In this study, Rg3 significantly dose-dependently suppressed the viability, migration, invasion, angiogenesis, and protein expressions of N-cadherin, vimentin, COX2, and VEGF in H1299 and A549 cells, while promoting the expression of E-cadherin protein. COX2 overexpression markedly reversed the effects of Rg3 on the viability, migration, invasion, angiogenesis, and EMT-related protein expression levels in LC cells; however, such effects of COX2 overexpression were offset by VEGF knockdown. In sum, Rg3 alleviates the migration, invasion, and angiogenesis of LC cells by inhibiting the expressions of COX2 and VEGF.

Topics: Cell Line; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cyclooxygenase 2; Epithelial-Mesenchymal Transition; Ginsenosides; Humans; Lung Neoplasms; Vascular Endothelial Growth Factor A

Lung cancer is one of the most common cancers and the leading cause of cancer-related deaths in the world. Radiation is widely used for the treatment of lung cancer. However, radioresistance and toxicity limit its effectiveness. Ginsenoside Rg3 (Rg3) is a positive monomer extracted from ginseng and has been shown to the anti-cancer ability on many tumors. The aim of the present study was to ascertain whether Rg3 is able to enhance the radiosensitivity of lung cancer cells and investigate the underlying mechanisms. The effect of Rg3 on cell proliferation was examined by Cell Counting Kit-8 (CCK-8) and radiosensitivity was measured by colony formation assay. Flow cytometry, transwell, and wound healing assay were used to determine apoptosis, cell cycle, and metastasis. Western blot was used to detect the main protein levels of the PI3K/AKT signaling pathway. We found that Rg3 inhibited cell proliferation, promoted apoptosis, and suppressed migration and invasion in radio-induced lung cancer cells. In addition, Rg3 increased the proportion of G2/M phase cells and inhibited the formation of cell colonies. Moreover, Rg3 decreased the expression levels of PI3K, p-AKT, and PDK1 in radio-induced cells. These findings indicate that Rg3 may be able to enhance the radiosensitivity in lung cancer cells by the PI3K/AKT signaling pathway. These results demonstrate the therapeutic potential of Rg3 as a radiosensitizer for lung cancer.

Topics: Animals; Apoptosis; Cell Line, Tumor; Cell Proliferation; Ginsenosides; Lung Neoplasms; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Radiation Tolerance; Signal Transduction

The most common cause of osteosarcoma (OS) death is lung metastasis. Currently, doxorubicin is the primary chemotherapy drug used to treat OS, however, it is not effective in inhibiting metastasis, and it has obvious cardiotoxicity. The anticancer activity of ginsenoside Rg3 has been demonstrated in a variety of malignant tumours. The aim of this study was to determine the potential role of ginsenoside Rg3 and doxorubicin in OS and the possible mechanism.. The potential synergistic effects of ginsenoside Rg3 and doxorubicin on human osteosarcoma cells 143B and U2OS, human umbilical vein endothelial cells, and mice receiving 143B xenografts and lung metastases were investigated.. Our study demonstrated that the combination of ginsenoside Rg3 and doxorubicin significantly inhibited cell proliferation, metastasis and angiogenesis in vitro. Mechanically, the anti-tumour activity of ginsenoside Rg3 and doxorubicin by modulating mTOR/HIF-1α/VEGF and EMT signalling pathways. Furthermore, ginsenoside Rg3 combined with doxorubicin inhibits tumour growth and lung metastasis in 143B-derived murine osteosarcoma models. More importantly, ginsenoside Rg3 can effectively ameliorate doxorubicin-induced weight loss and cardiotoxicity in mice.. Consequently, we concluded that the combination of ginsenoside Rg3 and doxorubicin displayed an evidently synergistic effect, which has the potential to be used as an effective and safe therapeutic approach for OS treatment.

Topics: Animals; Bone Neoplasms; Cardiotoxicity; Cell Line, Tumor; Cell Proliferation; Doxorubicin; Endothelial Cells; Ginsenosides; Humans; Lung Neoplasms; Mice; Osteosarcoma; TOR Serine-Threonine Kinases; Vascular Endothelial Growth Factor A

Chemotherapy is a commonly used strategy for advanced lung cancer patients. However, its clinical application is restrained due to its toxicity and drug resistance. Ginsenoside Rg3 (Rg3) has a strong anticancer influence on colon cancer, breast cancer, lung cancer, and other malignant tumors. However, it is still unclear whether Rg3 can cooperate with 5-FU to inhibit the tumor growth and angiogenesis of lung adenocarcinoma (LUAD). This study examined the combined treatment of Rg3 and 5-FU in LUAD. It was revealed that the combined treatment could notably enhance the suppression on proliferative, invasive, and migratory abilities and angiogenesis in LUAD cells A549 and SPC-A-1. On the other hand, we also discovered that Rg3 or 5-FU could suppress the activity of the NF-

Topics: Adenocarcinoma of Lung; Cell Line, Tumor; Fluorouracil; Ginsenosides; Humans; Lung Neoplasms

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Topics: Cell Line, Tumor; Cell Proliferation; Epithelial-Mesenchymal Transition; Ginsenosides; Hedgehog Proteins; Humans; Lung Neoplasms; Signal Transduction

Lung cancer is the leading cause of cancer death in the world and classified into non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). As tyrosine kinase inhibitors (TKIs), several triterpenoid saponins can target to epidermal growth factor receptor (EGFR), a widely used molecular therapeutic target, to exhibit remarkable anti-proliferative activities in cancer cells. As one of triterpenoid saponins, 20([Formula: see text])-ginsenoside Rg3 [20([Formula: see text])-Rg3] was confirmed to be an EGFR-TKI in this work. According to the quantitative real-time reverse transcription-PCR (qRT-PCR) and immunoblotting analysis, 20([Formula: see text])-Rg3 was certified to play a key role on EGFR/Ras/Raf/MEK/ERK signal pathway regulation. Our data demonstrated that 20([Formula: see text])-Rg3 might block the cell cycle at the G0/G1 phase by downregulating CDK2, Cyclin A2, and Cyclin E1. Molecular docking suggested that the combination of both hydrophobic and hydrogen-bonding interactions may help stabilizing the 20([Formula: see text])-Rg3-EGFR binding. Furthermore, their binding stability was assessed by molecular dynamics simulation. Taken together, these data provide the evidence that 20([Formula: see text])-Rg3 could prohibit A549 cell proliferation, probably by arresting the cell cycle at the G0/G1 phase via the EGFR/Ras/Raf/MEK/ERK pathway.

Topics: A549 Cells; Carcinoma, Non-Small-Cell Lung; Cell Cycle; Cell Proliferation; ErbB Receptors; Ginsenosides; Humans; Lung Neoplasms; MAP Kinase Signaling System; Molecular Targeted Therapy; Phytotherapy; raf Kinases; ras Proteins

In the present study, we found that Ginsenoside Rg3 attenuated the stemness of non-small cell lung cancer (NSCLC) cells, evident by decreasing spheroid formation ability, ALDH1 activity and stemness marker expression. Furthermore, osimertinib-resistant NSCLC cells displayed a stronger stemness than the parental cells. Ginsenoside Rg3 reduced the stemness and osimertinib resistance of osimertinib-resistant cells. RNA-sequencing revealed that Hippo signaling was shown on the top of the most upregulated pathways regulated by Ginsenoside Rg3 in NSCLC cells, and YAP/TAZ expression was suppressed by Ginsenoside Rg3. Notably, the inhibitor of Hippo signaling attenuated the effects of Ginsenoside Rg3 on the stemness of NSCLC cells. Therefore, Ginsenoside Rg3 attenuates the osimertinib resistance of NSCLC cells via suppressing the stemness, which is dependent on Hippo pathway.

Topics: Acrylamides; Aniline Compounds; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Drug Resistance, Neoplasm; Ginsenosides; Hippo Signaling Pathway; Humans; Lung Neoplasms; Neoplastic Stem Cells; Protein Serine-Threonine Kinases; Signal Transduction

Lung cancer is the leading cause of cancer-related deaths. Ginsenoside Rg3 is the main ingredient of Ginseng which is used to treat non-small cell lung cancer (NSCLC). It has been found to enhance the efficiency of chemotherapy thereby reducing its side effects. Previous studies found that ginsenoside Rg3 can reduce the occurrence of NSCLC by inducing DNA damage. Yet, its anti-DNA damaging effects and mechanisms in tumor cells are still not fully understood. This study explored the effect of ginsenoside Rg3 on DNA repair and VRK1/P53BP1 signaling pathway. Ginsenoside Rg3 treatment significantly decreased the incidence and invasionin a mouse model of lung cancer induced by urethane. The results of cell survival assay and single cell gel electrophoresis showed that ginsenoside Rg3 protected lung adenocarcinoma cells from DNA damage as well as inhibited the proliferation of tumor cells. Ginsenoside Rg3 increased the mRNA and protein expression of VRK1 in NSCLC cells as measured by RT-qPCR and western blot, respectively. These findings suggests that ginsenoside Rg3 regulates VRK1 signaling. Immunofluorescence assays showed that P53BP1 and VRK1 protein level increased, and the VRK1 protein translocated between the nuclei and cytoplasm. Finally, this conclusion was confirmed by the reverse validation in VRK1-knockdown cells. Taken together, these results show that ginsenoside Rg3 upregulate VRK1 expression and P53BP1 foci formation in response to DNA damage thereby inhibiting the tumorigenesis and viability of cancer cells. These findings reveal the role of Rg3 in lung cancer and provides therapeutic targets for developing new drugs in the prevention and treatment of lung cancer.

Topics: A549 Cells; Animals; Apoptosis; Carcinogenesis; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Nucleus; Cell Survival; Cytoplasm; DNA Damage; Ginsenosides; Humans; Lung Neoplasms; Male; Mice; Mice, Inbred C57BL; Panax; Protein Serine-Threonine Kinases; RNA, Messenger; Signal Transduction; Tumor Suppressor p53-Binding Protein 1; Up-Regulation

PTX3, a member of the long pentraxin subfamily, associated with innate immunity is indispensable for resistance to some cancer. Gemcitabine, an analog of cytosine arabinoside, has shown restrained benefits because of profound chemoresistance. The PTX3 expression on GEM in human lung cancer cells have not yet been clarified; the present study aimed to show reactive oxygen species (ROS) mediatory PTX3 expression through distinct mechanisms. Whereas ginsenoside Rg3 is a herbal medicine with strong antitumor activity. Furthermore, we tested the hypothesis; Rg3 abrogates GEM-induced production of ROS-mediated activation of Akt and extracellular signal-regulated kinase (ERK) pathways and inhibits nuclear piling-up of nuclear factor kappa B (NF-κB) and HIF-1α. On the basis of time and dose-dependent manner, our data demonstrated that GEM-induced PTX3 expression was dependent on ROS generation as it was abrogated by pretreatment of lung cancer cells with the free radical scavenger N-acetyl-l-cysteine. Our data demonstrated that PTX3 upregulation by GEM correlated with the time-dependent escalation of NF-κB and HIF-1α in the nucleus resulted from phosphorylation-induced degradation of IκBα, whereas HIF-1α upregulation was NF-κB-dependent. Increase in ROS expression in lung cancer cells on GEM treatment preceded the nuclear accumulation of NF-κB and HIF-1α and suppression of ROS diminished these effects. ERK1/2 and Akt activation mediated the effect of ROS on NF-κB and HIF-1α and their pharmacological inhibition suppressed GEM-induced PTX3. Our study findings reinforced the role regarding PTX3 signaling in GEM-induced resistance and pointed toward an unintended and undesired effect of chemotherapy and to get an active regimen; the synergy was associated with NF-κB downregulation in lung cancer.

Topics: A549 Cells; C-Reactive Protein; Cell Movement; Deoxycytidine; Drug Resistance, Neoplasm; Gemcitabine; Gene Expression Regulation, Neoplastic; Ginsenosides; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Lung Neoplasms; MAP Kinase Signaling System; Neoplasm Invasiveness; NF-kappa B; NF-KappaB Inhibitor alpha; Phosphorylation; Proto-Oncogene Proteins c-akt; Reactive Oxygen Species; Serum Amyloid P-Component; Signal Transduction

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have become a standard therapy for non-small cell lung cancer (NSCLC) patients with sensitive mutations. However, acquired resistance inevitably emerges after a median of 6-12 months. It has been demonstrated that autophagy plays an important role in EGFR-TKI resistance. 20(S)-ginsenoside Rg3 (Rg3) is proposed to sensitize the cancer cells to chemotherapy by inhibiting autophagy. We examined the ability of Rg3 to inhibit autophagy and increase the sensitivity of NSCLC cells to icotinib. We show that the induction of autophagy in response to icotinib contributes to the development of icotinib resistance. Rg3 is capable of inhibiting autophagic flux and enhancing the sensitivity of NSCLC cells to icotinib. The resistance to icotinib could also be reversed through Rg3-induced autophagy inhibition. Autophagy inhibition by Rg3 increases the therapeutic response in both icotinib-sensitive and icotinib-resistant NSCLC cells with an EGFR-activating mutation and may be an effective new treatment strategy for this disease.

Topics: Animals; Autophagy; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Proliferation; Crown Ethers; Drug Synergism; Female; Ginsenosides; Humans; Lung Neoplasms; Mice; Mice, Inbred BALB C; Quinazolines; Xenograft Model Antitumor Assays

Ginsenosides have previously been demonstrated to effectively inhibit cancer cell growth and survival in both animal models and cell lines. However, the specific ginsenoside component that is the active ingredient for cancer treatment through interaction with a target protein remains unknown. By an integrated quantitative proteomics approach via affinity mass spectrum (MS) technology, we deciphered the core structure of the ginsenoside active ingredient derived from crude extracts of ginsenosides and progressed toward identifying the target protein that mediates its anticancer activity. The Tandem Mass Tag (TMT) labeling quantitative proteomics technique acquired 55620 MS/MS spectra that identified 5499 proteins and 3045 modified proteins. Of these identified proteins, 224 differentially expressed proteins and modified proteins were significantly altered in nonsmall cell lung cancer cell lines. Bioinformatics tools for comprehensive analysis revealed that the Ras protein played a general regulatory role in many functional pathways and was probably the direct target protein of a compound in ginsenosides. Then, affinity MS screening based on the Ras protein identified 20(s)-protopanaxadiol, 20(s)-Ginsenoside Rh2, and 20(s)-Ginsenoside Rg3 had affinity with Ras protein under different conditions. In particular, 20(s)-protopanaxadiol, whose derivatives are the reported antitumor compounds 20(s)-Ginsenoside Rh2 and 20(s)-Ginsenoside Rg3 that have a higher affinity for Ras via a low KD of 1.22 μM and the mutation sites of G12 and G60, was demonstrated to play a core role in those interactions. Moreover, the molecular mechanism and bioactivity assessment results confirmed the identity of the chemical ligand that was directly acting on the GTP binding pocket of Ras and shown to be effective in cancer cell bioactivity profiles.

Topics: Animals; Antineoplastic Agents, Phytogenic; Carcinoma, Non-Small-Cell Lung; Cell Cycle; Cell Line, Tumor; Cell Survival; Ginsenosides; Guanosine Triphosphate; Humans; Lung Neoplasms; Molecular Docking Simulation; Neoplasm Proteins; Protein Binding; Protein Conformation; Proteomics; ras Proteins; Sapogenins

Cisplatin is a first line chemotherapy in lung cancer, but decreased susceptibility may limit its application. In solid tumors, hypoxia alters the microenvironment and is associated with proliferation, metastasis, and drug sensitivity. The hypoxia-induced desensitization of cisplatin is not clearly elucidated. 20 (R)-Ginsenoside (Rg3), the traditional Chinese medicine, is extracted from ginseng and has antitumor activities. In this study, we evaluated if Rg3 is effective in improving cisplatin sensitivity by blocking hypoxia. We found that the inhibition of proliferation potential by cisplatin was reduced in cobalt chloride (CoCl

Topics: A549 Cells; Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cell Hypoxia; Cell Line, Tumor; Cisplatin; Epithelial-Mesenchymal Transition; Ginsenosides; Humans; Hypoxia; Lung Neoplasms; Male; Mice, Inbred BALB C; Mice, Nude; Molecular Structure; Neoplastic Stem Cells; NF-kappa B; Tumor Burden; Xenograft Model Antitumor Assays

Ginsenoside Rg3, a bioactive constituent from Panax ginseng, is a worldwide well-known traditional Chinese medicine used as a tonic. It also has good antitumor activity by inhibiting tumors metastasis. Tumor metastasis is a high risk in thyroid cancer. However, the effect and molecular mechanism underlying the antimetastatic activity of Rg3 in thyroid cancer have not been reported. In our study, we found that Rg3 inhibited the growth of thyroid cancer in vitro and in vivo and significantly inhibited metastasis of thyroid cancer. Rg3 apparently inhibited the migration and invasion in four papillary thyroid cancer (PTC) cells (TPC-1, BCPAP, C643, and Ocut-2c cells) and pulmonary metastasis in lung metastasis model of C643 cells in nude mice. We further found that a possible mechanism of Rg3 inhibiting thyroid cancer cells metastasis was associated with inhibiting cells actin skeleton function. Rg3 inhibited lamellipodia formation and induced microspike formation by inhibiting Rho GTPase in thyroid cancer cells. Rg3 decreased the levels of Rac-1 and Cdc42 proteins. In addition, Rg3 decreased the expression levels of matrix metalloproteinase-2 (MMP-2) and MMP-9 proteins in four thyroid cancer cells. The results that Rg3 remarkably inhibited the expression of vascular endothelial growth factor-C (VEGF-C) protein in PTC cells and VEGF-A protein in anaplastic thyroid cancer (ATC) cells and decreased the staining of CD31 in PTC and ATC tumors hinted that Rg3 might inhibit the lymph node metastasis in PTC and angiogenesis in ATC. These studies suggested that Rg3 might be a useful agent for the treatment of metastatic thyroid cancers.

Topics: Actins; Animals; Antineoplastic Agents, Phytogenic; cdc42 GTP-Binding Protein; Cell Line, Tumor; Cell Movement; Female; Ginsenosides; Humans; Lung Neoplasms; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Mice; Mice, Inbred C57BL; Mice, Nude; Neoplasm Metastasis; Panax; rac1 GTP-Binding Protein; Thyroid Neoplasms; Vascular Endothelial Growth Factor A

Programmed death ligand 1 (PD-L1) as one the most important immune checkpoint was verified to involve in chemotherapy resistance in non-small cell lung cancer (NSCLC). Ginsenoside Rg3 is isolated from Chinese herb-Panax ginseng which is recognized to boost immune and has anti-cancer activity against a majority of carcinomas including NSCLC. In this study, we aim to identify whether Rg3 could attenuate the PD-L1 expression induced by resistance to cisplatin and draw out the underlying mechanisms of PD-L1 in this process. Human lung cancer cell lines A549 and A549/DDP (cisplatin-resistance) were used. Cell viability was detected by MTT assay, the PD-L1, Akt and NF-κB p65 protein expression were detected using Western blot analysis, the T cells cytotoxity to tumor cells was detected by crystal violet staining living residual tumor cells after coculture of tumor cells and T cells. The results showed that Rg3 could inhibit the growth and alleviate the resistant to cisplatin of A549/DDP cells. PD-L1 was overexpression in A549/DDP cells than A549 cells. Rg3 could decrease the PD-L1 expression induced by chemoresistance and resume the T cells cytotoxity to cancer cells. NF-κB p65 and Akt were involved in the PD-L1 overexpression and restrained by Rg3. Therefore, Rg3 could be regarded as a new agent targeting PD-L1 in chemotherapy refractory NSCLC.

Topics: A549 Cells; B7-H1 Antigen; Cisplatin; Coculture Techniques; Dose-Response Relationship, Drug; Down-Regulation; Drug Resistance, Neoplasm; Ginsenosides; Humans; Leukocytes, Mononuclear; Lung Neoplasms

Lung cancer is recognized as the most prevalent type of cancer with high death rate. Ginsenoside Rg3 isolated from Traditional Chinese Medicine Panax Ginseng has significant anticancer effects on many tumors. In this study, the effects of ginsenoside Rg3 on cells viability, apoptosis and PI3K/Akt signaling pathway in lung cancer cells were investigated in vitro and in vivo. In vitro, the viability of lung cancer cell lines A549，H23 was examined by CCK-8 kits; The proportion of cell apoptosis was measured by flow cytometry. The expression of p-PI3K/PI3K and p-Akt/Akt was evaluated with Western blot. In vivo, A549，H23 cells were subcutaneously injected into the nude mice. Histopathological analysis was stained with HE, and TUNEL assay was used to detect cell apoptosis. The results showed that Rg3 obviously inhibited cell viability, induced apoptosis and inhibited PI3K/Akt signalling pathway on A549, H23 cells in vitro and in vivo. Rg3 effectively inhibited the volume and weight of tumor in xenografts model, which may be related with inhibiting PI3K/Akt signaling pathways.

Topics: Adenocarcinoma; Animals; Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Dose-Response Relationship, Drug; Gene Expression Regulation; Ginsenosides; Humans; Lung Neoplasms; Mice; Mice, Nude; Neoplasms, Experimental; Phosphatidylinositol 3-Kinases; Phytotherapy; Proto-Oncogene Proteins c-akt; Signal Transduction

The epithelial-mesenchymal transition (EMT) is an important factor in lung cancer metastasis, and targeting EMT is a potential therapeutic strategy. Fucosyltransferase IV (FUT4) and its synthetic cancer sugar antigen Lewis Y (LeY) was abnormally elevated in many cancers. In this study, a traditional Chinese medicine ginsenoside Rg3 was used to investigate whether its inhibition to EMT and invasion of lung cancer is by the glycobiology mechanism. We found that Rg3 treatment (25, 50, 100 μg/ml) inhibited cell migration and invasion by wound-healing and transwell assays. Rg3 could significantly alter EMT marker proteins with increased E-cadherin, but decreased Snail, N-cadherin and Vimentin expression. Rg3 also down-regulated FUT4 gene and protein expression in lung cancer cells by qPCR, Western blot and immunofluorescence. After FUT4 down-regulated with shFUT4, EMT was obviously inhibited. Furthermore, the activation of EGFR through decreased LeY biosynthesis was inhibited, which blocked the downstream MAPK and NF-κB signal pathways. In addition, Rg3 reduced tumor volume and weight in xenograft mouse model, and significantly decreased tumor metastasis nodules in lung tissues by tail vein injection. In conclusion, Rg3 inhibits EMT and invasion of lung cancer by down-regulating FUT4 mediated EGFR inactivation and blocking MAPK and NF-κB signal pathways. Rg3 may be a potentially effective agent for the treatment of lung cancer.

Topics: A549 Cells; Animals; Blotting, Western; Cadherins; Cell Movement; Down-Regulation; Epithelial-Mesenchymal Transition; Fucosyltransferases; Gene Expression Regulation, Neoplastic; Ginsenosides; Humans; Immunohistochemistry; Lewis X Antigen; Lung Neoplasms; Male; Mice, Inbred BALB C; Mice, Nude; Neoplasm Invasiveness; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; Vimentin; Xenograft Model Antitumor Assays

To comparatively observe the effects of 20(R)-ginsenoside Rg3 and PEG-PLGA-Rg3 nanoparticles on the Lewis lung cancer mice and to explore the mechanisms of Rg3 and PEG-PLGA-Rg3 nanoparticle anti-cancer in vivo.. Lewis lung cancer mouse model was established and 60 mice were randomly divided into 5 groups with twelve in each group: PEG-PLGA-Rg3 nanoparticles group(Rg3-N), PEG-PLGA group (PEG), Rg3 group (Rg3), normal control group(C), saline control group(NS), and received intragastric administration for 14 days. The weights of the mice were measured every 2 days and the weight curves were obtained. At the same time, the color pattern, activity and mental status were observed. The mice were sacrificed when the administration was over, and the effects of 20(R)-ginsenoside Rg3 and PEG-PLGA-Rg3 nanoparticles on tumor weight, and the tumor:weight ratios were analysed. In addition, the tumor microvessel density (MVD) was measured by immunohistochemical staining with anti-CD31 antibody to compare the effects of Rg3 and PEG-PLGA-Rg3 nanoparticles on the tumor angiogenesis in vivo. Furthermore, the levels of such angiogenesis and proliferation factors as MMP-9, HIF-1α, VEGF, Ki-67 were examined by RT-PCR, Western blot and immunohistochemistry to explore the internal molecular mechanisms of anti-tumor effects in vivo.. The trends of variation of the mice weights in NS group and PEG group were rising early but declining later. In contrast, the trends of the other three groups were rising early and became stable later. In comparison with NS group, the mice of Rg3 group and Rg3-N group had better general status: brighter color, more active and better spirit. Compared with NS group,the tumor weight in PEG group, Rg3 group and Rg3-N group showed no significant difference but the tumor:weight ratio and MVD in Rg3 group and Rg3-N group declined significantly (P<0.01). Besides, there was no significant difference between Rg3 group and Rg3-N group. At the same time, the level of VEGF mRNA, the protein expression of MMP-9, HIF-1α, VEGF in Rg3 group and Rg3-N group decreased compared with NS group. Furthermore, the level of each index above-mentioned in Rg3-N group was lower than that in Rg3 group. The expression of Ki-67 in PEG group, Rg3 group and Rg3-N group showed no significant difference compared with NS group.. Rg3 and PEG-PLGA-Rg3 nanoparticle may suppress the expression of VEGF, MMP-9 and HIF-1α in Lewis lung cancer mice, thereby indirectly contributing to their antitumor effects and alleviating the mice's general status. In addition, PEG-PLGA nanoparticles embedding can promote Rg3 antitumor effect in vivo.

Topics: Animals; Disease Models, Animal; Ginsenosides; Hypoxia-Inducible Factor 1, alpha Subunit; Ki-67 Antigen; Lung Neoplasms; Matrix Metalloproteinase 9; Mice; Nanoparticles; Neovascularization, Pathologic; Polyesters; Polyethylene Glycols; Vascular Endothelial Growth Factor A

Acquired resistance is a bottleneck that restricts the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) for lung cancer. Ginsenoside Rg3 is an antiangiogenic agent which can down-regulate the expressions of vascular endothelial growth factor (VEGF) and EGFR. Combination of EGFR-TKI and ginsenoside Rg3 may be a promising strategy to delay acquired resistance. This retrospective study explored the efficacy and safety of this combined regimen in patients with EGFR mutation and advanced non-small cell lung cancer (NSCLC).. By the deadline of March 31th 2016, the median follow-up period reached 22.9 months. The median PFS was significantly longer in group A than in group B (12.4 months vs 9.9 months, P = 0.017). In addition, ORR was significantly higher in group A than in group B (59.6% vs 41.7%, P = 0.049). The median OS in group A showed no extended tendency compared with that in group B (25.4 months vs 21.4 months, P = 0.258). No significant difference in side effects was found between the two groups.. A total of 124 patients with advanced NSCLC and EGFR active mutation were collected and analyzed. All of them were treated with first-line EGFR-TKI and divided into two groups. In group A (n=52), patients were administered EGFR-TKI plus ginsenoside Rg3 at standard doses. In group B (n=72), patients received EGFR-TKI alone. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and side effects were analyzed.. Ginsenoside Rg3 improves median PFS and ORR of first-line EGFR-TKI treatment in EGFR-mutant advanced NSCLC patients, thus providing a new regimen to delay acquired resistance of EGFR-TKI.

Topics: Adult; Aged; Aged, 80 and over; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; ErbB Receptors; Exanthema; Female; Ginsenosides; Humans; Lung Neoplasms; Male; Middle Aged; Mutation; Protein Kinase Inhibitors; Retrospective Studies; Vascular Endothelial Growth Factor A

Ginsenoside Rg3 (Rg3), a pharmacologically active compound from red ginseng, has been reported to induce cell death in various cancer cell lines, although the specific mechanisms have not been well established. In the present study, Rg3 treatment to A549 human lung adenocarcinoma led to cell death via not only apoptotic pathways but also the downregulation of epidermal growth factor receptor (EGFR). We used cross-linker and cell enzyme-linked immunosorbent assays to show that Rg3 inhibited EGFR dimerization by EGF stimulation and caused EGFR internalization from the cell membrane. Among several important phosphorylation sites in cytoplasmic EGFR, Rg3 increased the phosphorylation of tyrosine 1045 (pY1045) and serine 1046/1047 (pS1046/1047) for EGFR degradation and coincidently, attenuated pY1173 and pY1068 for mitogen-activated protein kinase activity. These effects were amplified under EGF-pretreated Rg3 stimulation. In vivo experiments showed that the average volume of the tumors treated with 30 mg/kg of Rg3 was significantly decreased by 40% compared with the control. Through immunohistochemistry, we detected the fragmentation of DNA, the accumulation of Rg3, and the reduction of EGFR expression in the Rg3-treated groups. Here, we provide the first description of the roles of Rg3 in the reduction of cell surface EGFR, the attenuation of EGFR signal transduction, and the eventual activation of apoptosis in A549 human lung adenocarcinoma.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Cell Line, Tumor; Down-Regulation; ErbB Receptors; Ginsenosides; Humans; Lung; Lung Neoplasms; Male; Mice, Inbred C57BL; Panax; Protein Multimerization; Proteolysis

The epithelial-mesenchymal transition (EMT) is a pivotal cellular process during which epithelial polarized cells become motile mesenchymal-appearing cells, which, in turn, promotes the metastatic potential of cancer. Ginseng is a perennial plant belonging to the genus Panax that exhibits a wide range of pharmacological and physiological activities. Ginsenosides 20-Rg3, which is the active component of ginseng, has various medical effects, such as anti-tumorigenic, anti-angiogenesis, and anti-fatiguing activities. In addition, ginsenosides 20(S)-Rg3 and 20(R)-Rg3 are epimers, and this epimerization is produced by steaming. However, the possible role of 20(S)-Rg3 and 20(R)-Rg3 in the EMT is unclear. We investigated the effect of 20(S)-Rg3 and 20(R)-Rg3 on the EMT. Transforming growth factor-beta 1 (TGF-β1) induces the EMT to promote lung adenocarcinoma migration, invasion, and anoikis resistance. To understand the repressive role of 20(S)-Rg3 and 20(R)-Rg3 in lung cancer migration, invasion, and anoikis resistance, we investigated the potential use of 20(S)-Rg3 and 20(R)-Rg3 as inhibitors of TGF-β1-induced EMT development in A549 lung cancer cells in vitro. Here, we show that 20(R)-Rg3, but not 20(S)-Rg3, markedly increased expression of the epithelial marker E-cadherin and repressed Snail upregulation and expression of the mesenchymal marker vimentin during initiation of the TGF-β1-induced EMT. 20(R)-Rg3 also inhibited the TGF-β1-induced increase in cell migration, invasion, and anoikis resistance of A549 lung cancer cells. Additionally, 20(R)-Rg3 markedly inhibited TGF-β1-regulated matrix metalloproteinase-2 and activation of Smad2 and p38 mitogen activated protein kinase. Taken together, our findings provide new evidence that 20(R)-Rg3 suppresses lung cancer migration, invasion, and anoikis resistance in vitro by inhibiting the TGF-β1-induced EMT.

Topics: Anoikis; Blotting, Western; Cadherins; Cell Line, Tumor; Cell Movement; Cell Survival; Drug Resistance, Neoplasm; Enzyme Activation; Epithelial-Mesenchymal Transition; Ginsenosides; Humans; Lung Neoplasms; Matrix Metalloproteinase 2; Neoplasm Invasiveness; p38 Mitogen-Activated Protein Kinases; Real-Time Polymerase Chain Reaction; RNA; Smad2 Protein; Stereoisomerism; Transforming Growth Factor beta1; Vimentin; Wound Healing

Antitumor effects of a ginsenoside Rg(3)-fortified red ginseng preparation (Rg(3)-RGP) were investigated in human non-small cell lung carcinoma (H460) cells using in vitro cytotoxicity assay and in vivo nude mouse xenograft model. Immunomodulatory effects of the preparation were also assessed by measuring the facilitating activities on the nitric oxide (NO) release from peritoneal macrophages, in vitro and in vivo lymphocyte proliferation, and the carbon clearance from circulating blood. In a cell level, Rg(3)-RGP exerted H460 cytotoxicity and facilitated splenocyte proliferation at very high concentrations, without affecting NO production. However, oral administration of Rg(3)-RGP (100-300 mg/kg) enhanced carbon particle-phagocytic index of blood macrophages up to 360-397% of control value. In addition, Rg(3)-RGP significantly increased the splenocyte proliferation (23% at 100mg/kg). In tumor-bearing mice, 28-day oral treatment with Rg(3)-RGP (100mg/kg) remarkably suppressed the tumor growth, leading to the decrease of the tumor volume and weight by 30-31%, which was comparable to the effect (27-29% reduction) of doxorubicin (2mg/kg at 3-day intervals). While Rg(3)-RGP did not cause adverse effects, intravenous injection of doxorubicin markedly decreased body and testes weights, and exhibited severe depletion of spermatogenic cells in the atrophic seminiferous tubules. These results indicate that Rg(3)-RGP exerts antitumor activities via indirect immunomodulatory actions, without causing adverse effects as seen in doxorubicin.

Topics: Adjuvants, Immunologic; Animals; Antibiotics, Antineoplastic; Antineoplastic Agents, Phytogenic; Body Weight; Carbon; Cell Line, Tumor; Cell Proliferation; Doxorubicin; Ginsenosides; Heart; Humans; Lung Neoplasms; Lymphocytes; Macrophages, Peritoneal; Male; Mice; Mice, Inbred BALB C; Mice, Inbred ICR; Neoplasm Transplantation; Nitric Oxide; Organ Size; Panax; Plant Preparations; Spleen; Testis

Ginsenoside Rg3, a saponin extracted from ginseng, inhibits angiogenesis. The combination of low-dose chemotherapy and anti-angiogenic inhibitors suppresses growth of experimental tumors more effectively than conventional therapy or anti-angiogenic agent alone. The present study was designed to evaluate the efficacy of low-dose gemcitabine combined with ginsenoside Rg3 on angiogenesis and growth of established Lewis lung carcinoma in mice.. C57L/6 mice implanted with Lewis lung carcinoma were randomized into the control, ginsenoside Rg3, gemcitabine and combination group. The quality of life and survival of mice were recorded. Tumor volume, inhibitive rate and necrosis rate were estimated. Necrosis of tumor and signals of blood flow as well as dynamic parameters of arterial blood flow in tumors such as peak systolic velocity (PSV) and resistive index (RI) were detected by color Doppler ultrasound. In addition, expression of vascular endothelial cell growth factor (VEGF) and CD31 were observed by immunohistochemstry, and microvessel density (MVD) of the tumor tissues was assessed by CD31 immunohistochemical analysis.. Quality of life of mice in the ginsenoside Rg3 and combination group were better than in the control and gemcitabine group. Combined therapy with ginsenoside Rg3 and gemcitabine not only enhanced efficacy on suppression of tumor growth and prolongation of the survival, but also increased necrosis rate of tumor significantly. In addition, the combination treatment could obviously decrease VEGF expression and MVD as well as signals of blood flow and PSV in tumors.. Ginsenoside Rg3 combined with gemcitabine may significantly inhibit angiogenesis and growth of lung cancer and improve survival and quality of life of tumor-bearing mice. The combination of chemotherapy and anti-angiogenic drugs may be an innovative and promising therapeutic strategy in the experimental treatment of human lung cancer.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Lewis Lung; Cell Growth Processes; Deoxycytidine; Female; Gemcitabine; Ginsenosides; Humans; Lung Neoplasms; Mice; Mice, Inbred BALB C; Neovascularization, Pathologic; Random Allocation; Tumor Cells, Cultured; Vascular Endothelial Growth Factor A

To investigate the effect of ginsenoside Rg3 on the apoptosis and survivin expression in human lung squamous cell carcinoma cell line SK-MES-1.. SK-MES-1 cells were divided into Rg3 treatment group, blank control group and positive control (arsenic trioxide) group. The apoptotic rate of the cells in each group was determined using flow cytometry, and the expression of survivin protein and mRNA was detected by immunocytochemistry and RT-PCR, respectively.. A 48-h treatment with Ginsenoside Rg3 induced increased apoptotic rate of SK-MES-1 cells in a dose-dependent manner. Ginsenoside Rg3 significantly downregulated the expressions of survivin protein and mRNA as compared with the expression levels in the blank control group (P<0.05).. Ginsenoside Rg3 can induce the apoptosis of SK-MES-1 cells, the mechanism of which may involve inhibited survivin expression.

Topics: Apoptosis; Carcinoma, Squamous Cell; Cell Line, Tumor; Down-Regulation; Ginsenosides; Humans; Inhibitor of Apoptosis Proteins; Lung Neoplasms; Microtubule-Associated Proteins; RNA, Messenger; Survivin

To investigate the inhibitive effects of Ginsenosides Rg3 (GS-Rg3) in the process of tumor angiogenesis and the effects on the expressions of VEGF and its receptor KDR in human lung squamous cancer SK-MES-1 cell line.. Human lung cancer SK-MES-1 cells were cultured in vitro and immunocytochemistry and RT-PCR methods were used to detect the effects of different concentrations of Rg3 on the expressions of VEGF and KDR on SK-MES-1 cells.. The immunocytochemistry results showed that the positive rates of VEGF protein in different group of SK-MES-1 cells were 81.33 +/- 9.04, 61.80 +/- 7.98, 43.80 +/- 5.25, 29.77 +/- 8.04, respectively. The positive rates of KDR protein in different group of SK-MES-1 cells were 65.51 +/- 7.45, 51.73 +/- 9.21, 34.87 +/- 6.15, 22.04 +/- 5.11, respectively. There were significant differences between each group. RT-PCR results suggested that with the increase of the concentration of Rg3, VEGF and KDR amplified bands gradually weakened. There were significant differences between each group.. GS-Rg3 can down-regulate the expressions of KDR and VEGF protein and their mRNA in human lung squamous cancer SK-MES-1 cells. It may be one of the mechanisms in the process of inhibiting tumor angiogenesis.

Topics: Antineoplastic Agents, Phytogenic; Carcinoma, Squamous Cell; Cell Line, Tumor; Dose-Response Relationship, Drug; Ginsenosides; Humans; Immunohistochemistry; Lung Neoplasms; Neovascularization, Pathologic; Panax; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-2

Ginsenoside Rg3 is an effective chemical component extracted from the red Panix. The experiment demonstrated that it might effectively inhibit proliferation and metastasis of tumor cells. The exact molecular mechanism of Rg3 remains unclear so far. To further explore the antitumor function of Rg3, we investigated the in-vitro and in-vivo activity of Rg3 in the treatment of B16 melanoma cells, derived from C57BL/6 mouse, capable of forming tumor colonies in the lungs following intravenous injection. Cell proliferation was measured by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide assay. Morphological changes of cells were observed by staining with Giesma and Hoechst 33258. Cell cycle and apoptosis rate were analyzed by flow cytometry. The expression of caspase-3 and bcl-2 in cells was detected by immunocytochemistry and western blot analysis. We found that Rg3 could inhibit cell proliferation, regulate cell cycle, and induce cell apoptosis in vitro. B16 melanoma-bearing mice were used to evaluate in vivo the antitumor activity of Rg3. Mice that were injected with Rg3 showed significant inhibition of the tumor metastasis with lighter lung weight, lower density of microvessels, fewer metastasis nodules, and longer survival time than those in the control group (P<0.001). In conclusion, the results reveal that antitumor metastasis of Rg3 is also associated with inducing apoptosis, regulating cell cycle, and blocking angiogenesis in addition to inhibiting proliferation. This research might supply valuable data for chemotherapy with Rg3 in melanoma. Rg3 would turn out to be an anticancer drug with promising prospects.

Topics: Animals; Antineoplastic Agents; Apoptosis; Caspase 3; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Ginsenosides; Lung Neoplasms; Melanoma, Experimental; Mice; Mice, Inbred C57BL; Proto-Oncogene Proteins c-bcl-2; Skin Neoplasms

Ginsenosides are main components extracted from ginseng, and ginsenoside Rg3 is one of the most important parts. Ginsenoside Rg3 has been found to inhibit several kinds of tumor growth and metastasis. The present study was undertaken to investigate the effect of ginsenoside Rg3 on human ovarian cancer metastasis and the possible mechanism.. The experimental lung metastasis models of ovarian cancer SKOV-3 and the assay of tumor-induced angiogenesis were used to observe the inhibitory effects of Rg3 on tumor metastasis and angiogenesis. The effect of Rg3 on invasive ability of SKOV-3 cells in vitro was detected by Boyden chamber, and immunofluorescence staining was used to recognize the expression of matrix metalloproteinase 9 (MMP-9) in SKOV-3 cells.. In the experimental lung metastasis models of ovarian cancer, the number of tumor colonies in the lung and vessels oriented toward the tumor mass in each ginsenoside Rg3 group, was lower than that of control group. The invasive ability and MMP-9 expression of SKOV-3 cells decreased significantly after treatment with ginsenoside Rg3.. Ginsenoside Rg3 can significantly inhibit the metastasis of ovarian cancer. The inhibitory effect is partially due to inhibition of tumor-induced angiogenesis and decrease of invasive ability and MMP-9 expression of SKOV-3 cells.

Topics: Animals; Cell Line, Tumor; Female; Ginsenosides; Humans; Lung Neoplasms; Matrix Metalloproteinase 9; Mice; Neoplasm Invasiveness; Neovascularization, Pathologic; Ovarian Neoplasms

To assess the effect of 20(R)-Rg3 on the inhibition of angiogenesis of lung cancer and explore its role in the change of endogenous VEGF secreted by A549 tumor cells themselves.. A549 tumor cells were cultured with different concentrations of 20(R)-Rg3(10(-7) mol/L, 10(-6) mol/L, 10(-5) mol/L and 10(-4), mol/L), the VEGF contents were detected by ELASA method after 24 h, 48 h and 72 h. Cellular proliferation was detected by MTT method, and apoptosis was detected with flow cytometry.. It was found that Rg3 had no significant inhibitory effect on the proliferation of A549 cells. The apoptosis rate was 29.8% after the cells being interfered with Rg3 at 3 x 10(-5) mol/L for 120 h. The levels of VEGF in the groups of Rg3 at 10(-5) mol/L and 10(-4) mol/L were lower than that in the contrast group (P < 0.05). The level of VEGF in the group of 10(-4) mol/L was lower than that in the group of 10(-7) mol/L and group of 10(-6) mol/L, and it was lower after 72 h of interference than that after 24 h and 48 h of interfernce.. With the action of 20 (R)-Rg3, the level of VEGF secreted by A549 tumor cells themselves declined; the apoptosis of A549 tumor cells increased, especially at higher concentration and longer action time of Rg3. This might be one of the antiangiogenesis mechanisms of 20(R)-Rg3.

Topics: Angiogenesis Inhibitors; Apoptosis; Cell Line, Tumor; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Ginsenosides; Humans; Lung Neoplasms; Vascular Endothelial Growth Factor A

Topics: Angiogenesis Inhibitors; Animals; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Deoxycytidine; Drug Therapy, Combination; Female; Gemcitabine; Ginsenosides; Lung Neoplasms; Mice; Mice, Inbred C57BL; Neoplasm Transplantation

To study the effect of 20( R)-ginsenoside Rg3 on the expressions of angiogenesis factors proteins (VEGF,bFGF, MMP-2) in human lung adenocarcinoma cell line A549 and HUVEC304 cell.. The cell lines of A549 and HUVEC304 were cultured with 20(R)- Rg3. The gray scale and positive rate of VEGF, bFGF, MMP-2 were detected by immunohistochemistry. The differential expressions of genes were studied by DNA microarray.. The positive rate of VEGF protein in A549 cell decreased significantly as compared with the control group ( P = 0.03). The gray scales of VEGF, Flt, KDT proteins in both A549 cell lines and HUVEC 304 cell lines decreased ( P = 0.05). Gray scale of MMP-2 also decreased in A549 cell lines. The result of differential expressions of genes of A549 cell lines showed that 14 genes were down-regulated and 10 genes were up-regulated.. The Chinese materia medica of 20( R)-Rg3 can inhibit the expression of angiogenesis factors proteins via several target genes in both tumour cell and vascular endothelial cell.

Topics: Adenocarcinoma; Cell Line, Tumor; Endothelial Cells; Gene Expression Profiling; Ginsenosides; Humans; Lung Neoplasms; Matrix Metalloproteinase 2; Neovascularization, Pathologic; Oligonucleotide Array Sequence Analysis; Panax; Umbilical Veins; Vascular Endothelial Growth Factor A

To determine the effect of ginsenoside on the cellular proliferation, apoptosis and cell cycles in LC A549 and HUVEC 304 cell lines.. A549 and HUVEC 304 cell lines were cultured with different concentrations of ginsenoside. Cellular proliferation was detected with MTT, apoptosis and cell cycles were checked with Flow Cytometer, and change of microstructure was observed by transmission electron microscope.. The apoptosis rate was 29.8% in A549 cell lines after being interfered with ginsenoside at 3 x 10(-6) mol/L, significantly higher than that in the control group ( P < 0.05). No change was observed in the cell cycles after being interfered with ginsenoside. The inhibitive rate of ginsenoside was 12.53% for HUVEC 304 cell line at 1 x 10(-4) mol/L (P < 0.05 ). The cells induced by conditioned medium could be inhibited by ginsenoside, and apoptotic body could be found in cells induced by conditioned medium at 10(-6) mol/L.. The proliferation of vascular endothelial cell could be inhibited by ginsenoside, and apoptosis could also be found in both tumor cells and cells induced by conditioned medium after being interfered with ginsenoside.

Topics: Adenocarcinoma; Antineoplastic Agents, Phytogenic; Apoptosis; Cell Cycle; Cell Line; Cell Line, Tumor; Cell Proliferation; Endothelial Cells; Ginsenosides; Humans; Lung Neoplasms; Umbilical Veins

To investigate the effect of ginsenoside-Rg3 on lung metastasis of ribonuclease inhibitor (RI) gene-transfected mouse B16 melanoma.. C57BL/6 mice were iv injected with parental or RI-transfected B16 melanoma cells. Lung metastasis was assessed by the number of surface tumor nodules. Mice were divided into 6 groups. Group I, II and III of mice were given parental, mock-transfected and RI-transfected B16 melanoma cells, respectively while in group IV, V and VI, Rg3 (1.5 mg/kg, iv q.o.d. x 10) was given to mice bearing parental, mock-transfected and RI-transfected B16 melanoma, respectively. Micovessel density (MVD) of the lung metastatic tumor was assessed by immunohistochemical staining of factor VIII-R expression.. The number of tumor nodules was significantly decreased in mice injected with RI-transfected B16 melanoma (Gp III, compared to Gp I and II). Rg3 treatment per se could also decrease the number of lung tumor nodules but to a lesser extent (Gp IV and V compared to Gp III). However, Rg3 synergized with RI transfection resulting in most significant inhibition of lung metastasis (Gp VI). Mice in Gp I and II died within 26 days of the experiment, whereas all the mice in Gp VI were alive during the observation period of one and one half month. MVD was significantly decreased in the lung tumor nodules in mice injected with RI-transfected B16 melanoma. It was further decreased when additional Rg3 was given (Gp VI).. Transfection of ribonuclease inhibitor gene significantly reduces the metastatic potential of B16 melanoma. Ginsenoside-Rg3 has a synergistic effect.

Topics: Animals; Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Ginsenosides; Lung Neoplasms; Male; Melanoma, Experimental; Mice; Mice, Inbred C57BL; Neoplasm Transplantation; Panax; Placental Hormones; Transfection

The effect of plant glycosides on tumor cell invasion was examined. Among the glycosides tested, ginsenoside Rg3 was found to be a potent inhibitor of invasion by rat ascites hepatoma cells (MM1), B16FE7 melanoma cells, human small cell lung carcinoma (OC10), and human pancreatic adenocarcinoma (PSN-1) cells, when examined in a cell monolayer invasion model. Structurally analogous ginsenosides, Rb2, 20(R)-ginsenoside Rg2 and 20(S)-ginsenoside Rg3 (a stereoisomer of Rg3), showed little inhibitory activity. Neither Rh1, Rh2, 20(R)-ginsenosides Rh1, Rb1, Rc nor Re had any effect. The effective ginsenoside, Rg3, tended to inhibit experimental pulmonary metastasis by highly metastatic mouse melanoma B16FE7 cells as well. Taking account of our previous finding that 1-oleoyl-lysophosphatidic add (LPA) induced invasion by MM1 cells in the monolayer invasion model, the effect of Rg3 on molecular events associated with the invasion induced by LPA was analyzed in order to understand the mechanism of the inhibition. Rg3, which suppressed the invasion induced by LPA, dose-dependently inhibited the LPA-triggered rise of intracellular Ca2+. Protein tyrosine phosphorylation triggered by LPA was not inhibited by Rg3.

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Carbohydrate Sequence; Carcinoma, Small Cell; Ginsenosides; Humans; Liver Neoplasms, Experimental; Lung Neoplasms; Lysophospholipids; Melanoma, Experimental; Mice; Mice, Inbred C57BL; Molecular Sequence Data; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Proteins; Pancreatic Neoplasms; Phosphorylation; Rats; Rats, Inbred Strains; Saponins; Tyrosine

We examined the inhibitory effect of two saponin preparations from Red ginseng, 20(R)- and 20(S)-ginsenoside-Rg3, in comparison with that of ginsenoside-Rb2, on lung metastasis produced by two highly metastatic tumor cells, B16-BL6 melanoma and colon 26-M3.1 carcinoma, in syngeneic mice. In an in vitro analysis, both saponin preparations showed a significant inhibition of adhesion to fibronectin (FN) and laminin (LM) by B16-BL6 melanoma. Similarly, they significantly inhibited the invasion of B16-BL6 cells into the reconstituted basement membrane (Matrigel)/FN in a dose-dependent manner. In an experimental metastasis model using B16-BL6 melanoma, consecutive intravenous (i.v.) administrations of 100 micrograms/mouse of 20(R)- or 20(S)-ginsenoside-Rg3 1, 2, 3 and 4 d after tumor inoculation led to a significant decrease in lung metastasis. The inhibitory effect of i.v. administration of both ginseng saponins on the tumor metastasis of B16-BL6 melanoma was also recognized in a low dose of 10 micrograms/mouse. The oral administration (p.o.) of both saponins (100-1000 micrograms/mouse) induced a significant decrease in lung metastasis of B16-BL6 melanoma. Moreover, both ginseng saponins were effective in inhibiting of lung metastasis produced by colon 26-M3.1 carcinoma. When 20(R)- or 20(S)-ginsenoside-Rg3 was orally administered consecutively after tumor inoculation in a spontaneous metastasis model using B16-BL6 melanoma, both of them significantly inhibited lung metastasis. In the experiment involving neovasculization by tumor cells in vivo, both mice groups given each saponin preparation after tumor inoculation exhibited a significant decrease in the number of blood vessels oriented toward the tumor mass, with no repression of tumor size. These findings suggest that both ginseng saponins, 20(R)- and 20(S)-ginsenoside-Rg3, possess an ability to inhibit the lung metastasis of tumor cells, and the mechanism of their antimetastatic effect is related to inhibition of the adhesion and invasion of tumor cells, and also to anti-angiogenesis activity.

Topics: Animals; Antineoplastic Agents; Cell Adhesion; Female; Ginsenosides; Lung Neoplasms; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Neoplasm Metastasis; Neovascularization, Pathologic; Panax; Plants, Medicinal; Saponins; Stereoisomerism; Tumor Cells, Cultured