ginsenoside-rg3 and Stomach-Neoplasms

To evaluate the enhancing effects of ginsenoside Rg3 combined with mitomycin C and tegafur (MF) on postoperative chemotherapy in advanced gastric cancer.. Seventy-one postoperative patients with advanced gastric cancer were randomly divided into two groups, the control group (n=33), which received treatment with only MF (Mitomycin C+Tegafur), and the trial group (n=38), which were treated with ginsenoside Rg3+MF. The serum VEGF levels in the control group and trial group were detected preoperatively and postoperatively, meanwhile, the serum VEGF levels in 30 healthy persons were detected as comparison. The relations between patients survival and serum VEGF levels were analyzed.. The levels of serum VEGF in advanced gastric cancer were higher than those in healthy persons [(297.8+/-129.6) pg/ml vs (212.3+/-67.5) pg/ml] (P<0.01), and were correlated with the depth of tumor invasion, lymph node metastasis, tumor size > 4 cm and TNM stage (P<0.05). Fourteen weeks after operation, the levels of serum VEGF in trial group decreased below those of preoperation and approached to normal range, while in the control group, the levels of serum VEGF decreased near those of preoperation only. The median survival of patients in trial group and control group were 40 and 25 months respectively. The survival rate of patients in trial group was significantly higher than that in control group (P=0.047).. The combined application of ginsenoside Rg3+MF chemotherapy can decrease the concentration of serum VEGF and improve the survival rate in advanced gastric cancer patients.

Topics: Adult; Aged; Aged, 80 and over; Angiogenesis Inhibitors; Chemotherapy, Adjuvant; Female; Ginsenosides; Humans; Male; Middle Aged; Mitomycin; Neoplasm Staging; Phytotherapy; Stomach Neoplasms; Survival Rate; Tegafur; Vascular Endothelial Growth Factor A

Ginsenoside Rg3 (GRg3) is a ginsenoside extracted from Panax ginseng. GRg3 displays multiple pharmacological properties, such as antitumor, anti-inflammatory, antioxidative and antifibrotic properties. However, whether GRg3 inhibits angiogenesis in gastric precancerous lesions (GPLs) and the possible mechanisms remain unknown. GRg3 attenuated gastric intestinal metaplasia and gastric dysplasia, the hallmark of GPL pathology, in rats with MNNG-ammonia compound induced GPLs. Increased CD34+ microvessel density and VEGF expression, which indicate the presence of angiogenesis, were evident in the rats with GPLs. GRg3 administration reduced VEGF protein expression and CD34+ microvessel density. In addition, GRg3 was capable of attenuating microvascular abnormalities. Data analysis revealed that enhanced protein expression of GLUT1, GLUT3 and GLUT4 were present in both human and animal GPL specimens. The administration of GRg3 caused significant decreases in the mRNA and protein expression levels of GLUT1 and GLUT4 in the rats with GPLs. However, the GRg3-treated rats with GPLs did not demonstrate regulatory effects on GLUT3, GLUT6, GLUT10, and GLUT12. Consistent with in vitro results, GRg3 administration significantly reduced the protein expression levels of GLUT1 and GLUT4 in both AGS and HGC-27 human gastric cancer cells in vitro. In conclusion, GRg3 can attenuate angiogenesis and temper microvascular abnormalities in rats with GPLs, which may be associated with its inhibition on the aberrant activation of GLUT1 and GLUT4.

Topics: Animals; Cell Line, Tumor; Down-Regulation; Ginsenosides; Glucose Transporter Type 1; Glucose Transporter Type 4; Humans; Male; Neovascularization, Pathologic; Precancerous Conditions; Rats; Rats, Sprague-Dawley; Retrospective Studies; Stomach Neoplasms

The aim of this study is to probe in the inhibitory effects of ginsenoside Rg3 on the expression of hypoxia-induced factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in human gastric cancer cells.. Human gastric cancer BGC823 cells were divided into the control group and experiment group, and expression levels of HIF-1α and VEGF were detected by immunocytochemistry and Western blot after cells were cultured under hypoxia for different durations.. Under hypoxia, expression of HIF-1α and VEGF in human gastric cancer BGC823 cells showed an increasing trend, and that was remarkably lower in experiment group than in the control group after applying Rg3, which was obvious at 12 and 24 h (P < 0.05).. Rg3 can inhibit expression of HIF-1α and VEGF in human gastric cancer cells and may influence abdominal implantation metastasis of gastric cancer through inhibiting its expression.

Topics: Antineoplastic Agents, Phytogenic; Cell Hypoxia; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Ginsenosides; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Immunohistochemistry; Stomach Neoplasms; Time Factors; Vascular Endothelial Growth Factor A

Helicobacter pylori (H. pylori) cytotoxin associated antigen A (CagA) plays a significant role in the development of gastric cancer. Ginsenoside Rg3 is a herbal medicine which inhibits cell proliferation and induces apoptosis in various cancer cells. Fucosylation plays important roles in cancer biology as increased fucosylation levels of glycoproteins and glycolipids have been reported in many cancers. Fucosyltransferase IV (FUT4) is an essential enzyme, catalyzes the synthesis of LewisY oligosaccharides and is regulated by specificity protein 1 (SP1) and heat shock factor protein 1 (HSF1) transcription factors. Herein, we studied the mechanism action of Rg3 apoptosis induction in gastric cancer cells. We treated the gastric cancer cells with CagA followed by Rg3, and analyzed their ability to induce apoptosis by evaluating the role of FUT4 as well as SP1 and HSF1 expressions by Western blot, flow cytometry and ELISA. We found that Rg3 significantly induced apoptosis in CagA treated gastric cancer cells, as evidenced by nuclear staining of 4-6-diamidino-2-phenylindole (DAPI) and Annexin-V/PI double-labeling. In addition, Rg3 significantly increased the expression of pro-apoptotic proteins and triggered the activation of caspase-3, -8, and -9 and PARP. Moreover, Rg3-induced apoptotic mechanisms indicated that Rg3 inhibited FUT4 expression through SP1 upregulation and HSF1 downregulation. Hence, Rg3 therapy is an effective strategy for gastric cancer treatment. Furthermore SP1 and HSF1 may serve as potential diagnostic and therapeutic targets for gastric cancer.

Topics: Antigens, Bacterial; Antineoplastic Agents; Apoptosis; Bacterial Proteins; Cell Line, Tumor; DNA-Binding Proteins; Fucosyltransferases; Ginsenosides; Heat Shock Transcription Factors; Humans; Lewis X Antigen; Sp1 Transcription Factor; Stomach Neoplasms; Transcription Factors

Ginsenosides play a role in a number of physiological and pharmacological functions in the gastrointestinal tract. The aim of this study was to clarify the potential role for transient receptor potential melastatin 7 (TRPM7) channels in ginsenoside Rg3-inhibited growth and survival of AGS cells, the most common human gastric adenocarcinoma cell line. The AGS cells were treated with varying concentrations of Rg3. Sub-G1 analysis, caspase-3 activity and poly(ADP-ribose) polymerase (PARP) cleavage analysis were conducted to determine whether AGS cell death occurs by apoptosis. TRPM7 channel blockers (La(3+) or 2-APB) and small interfering RNA (siRNA) were used in this study to confirm the role of TRPM7 channels. Furthermore, TRPM7 channels were over-expressed in human embryonic kidney (HEK) 293 cells to identify the role of TRPM7 channels in AGS cell growth and survival. The addition of Rg3 to the culture medium inhibited AGS growth and survival. Experimental results showed sub-G1 was markedly increased, caspase-3 activity was elevated, and degree of PARP cleavage was increased. TRPM7 channel blockade, either by La(3+) or 2-APB or by suppressing TRPM7 expression with siRNA, blocked the Rg3-induced inhibition of cell growth and survival. Furthermore, TRPM7 channel over-expression in HEK 293 cells exacerbated Rg3-induced cell death. These findings indicate that ginsenoside Rg3 inhibits the growth and survival of gastric cancer cell which is because of the blockade of TRPM7 channel activity. Therefore, TRPM7 channels may play an important role in the survival of gastric cancer.

Topics: Adenocarcinoma; Apoptosis; Cell Line, Tumor; Cell Survival; Drug Screening Assays, Antitumor; Gene Knockdown Techniques; Ginsenosides; Humans; Protein Serine-Threonine Kinases; RNA Interference; RNA, Small Interfering; Stomach Neoplasms; TRPM Cation Channels

To study the effect of angiogenesis inhibitor Rg3 on the growth and metastasis of gastric cancer in SCID mice.. Metastatic model simulating human gastric cancer was established by orthotopic implantation of histologically intact human tumor tissue into the gastric wall of SCID mice. Rg3 was administered by gastric perfusion at doses of 0, 2.5, 5.0, 10.0 mg/kg every day for 6 weeks 1 week after tumor implantation. One week after last administration, the mice were killed and their tumor weight was measured and the presence of metastasis recorded. Intratumoral microvessel density was examined by immunohistochemical staining with anti-CD31 monoclonal antibody.. Compared to the untreated controls, the growth of the orthotopically implanted tumor was significantly reduced in weight in mice treated with Rg3 with an inhibition rate of 52.3%, 63.3% and 71.6% at doses of 2.5, 5.0, 10.0 mg/kg, respectively. Tumor metastasis to the liver and peritoneum was also significantly inhibited in a dose-dependent manner. Decreased intratumoral microvessel density was noted in the treated mice.. Angiogenesis inhibitor Rg3 has strong inhibitory effect on tumor growth and metastasis of human gastric cancer in SCID mice.

Topics: Angiogenesis Inhibitors; Animals; Antineoplastic Agents; Female; Ginsenosides; Humans; Mice; Mice, SCID; Neoplasm Metastasis; Stomach Neoplasms