7-3--dihydroxy-4--methoxyisoflavone and Stomach-Neoplasms

Gastric cancer is a leading cause of cancer death worldwide. In-depth research of precancerous lesions of gastric carcinoma (PLGC) with malignant transformation potential is a key measure to prevent the development of gastric carcinoma. Recently, calycosin has been shown to have anticancer effects in vitro and in vivo. The molecular mechanism by which calycosin affects PLGC, however, has not yet been elucidated. The purpose of this study was to evaluate the effect and mechanism of calycosin in. The effects of calycosin in the gastric mucosa of rats with PLGC were evaluated using histopathology and transmission electron microscopy (TEM). For further characterization, the expression levels of integrin β1, nuclear factor kappa B (NF-κB), p-NF-κB, DARPP-32 and signal transducer and activator of transcription 3 (STAT3) were determined by Western blot assay and immunohistochemistry.. Hematoxylin-eosin and high iron diamine-Alcian blue-periodic acid-Schiff (HID-AB-PAS) staining showed that intestinal metaplasia and dysplasia were significantly ameliorated in the calycosin intervention groups compared with the model group. Further, TEM results showed that calycosin intervention tempered microvascular abnormalities and cell morphology of primary and parietal cells in PLGC tissues. The results suggested that calycosin had gastro-protective effects in MNNG-induced PLGC rats. Western blot and immunohistochemistry analysis showed that the increased protein expression levels of NF-κB, p-NF-κB, DARPP-32 and STAT3 in the model group were downregulated by calycosin. The upregulation of integrin β1 expression induced by MNNG was decreased in the calycosin groups.. Collectively, calycosin protected against gastric mucosal injury in part via regulation of the integrin β1/NF-κB/DARPP-32 pathway and suppressed the expression of STAT3 in PLGC. The elucidation of this effect and mechanism of calycosin in PLGC provides a potential therapeutic strategy for treatment of gastric precancerous lesions.

Topics: Administration, Oral; Animals; Isoflavones; Male; Molecular Conformation; Precancerous Conditions; Protective Agents; Rats; Rats, Sprague-Dawley; Stomach Neoplasms

Although diagnosis and treatment of gastric cancer have improved, the prognosis of patients remains poor. The majority of patients should be treated with chemotherapy or other follow-up treatment. However, the drug resistance of chemotherapy and heterogeneity of tumor itself lead to differences of sensitivity of chemotherapy drugs for different patients. Therefore, it is mandatory to develop better methods of treatment for treatment of gastric cancer. Calycosin has been used in several types of cancer cells. Cisplatin, 5-fluorouracil (5-FU), and adriamycin (ADM) are most widely used drugs for chemotherapy, and they improve the overall survival of cancer patients. To study whether and how calycosin enhances their inhibition of gastric cancer cells, we detected the signaling pathway in which calycosin and cisplatin, 5-FU, and ADM play role in human gastric cells lines. We found that calycosin can enhance the suppression of cisplatin to gastric cell line by inhibiting the phosphorylation of protein kinase B (Akt). So, when cisplatin/5-FU/ADM is combined with calycosin, it can achieve better therapeutic effect in lower concentration.

Topics: Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Apoptosis Regulatory Proteins; Cell Cycle Proteins; Cell Line, Tumor; Cell Proliferation; Cisplatin; Dose-Response Relationship, Drug; Doxorubicin; Drug Resistance, Neoplasm; Enzyme Activation; Fluorouracil; Humans; Isoflavones; Phosphorylation; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-akt; RNA Interference; Signal Transduction; Stomach Neoplasms; Time Factors; Transfection