Effects Of Ursolic Acid And A Cyclooxygenase-2 Inhibitor On Proliferation And Apoptosis Of Gastric Cancer Cells

Effects of ursolic acid and a cyclooxygenase-2 inhibitor on proliferation and apoptosis of gastric cancer cellsBackgroud Gastric cancer is one of the most common human malignant diseases and remains the leading cause of cancer-related mortality in our country. It is well known that cyclooxygenase-2 (COX-2) plays important roles in the carcinogenesis and progression of gastric cancer. Both ursolic acid and a special cyclooxygenase-2 (COX-2) inhibitor meloxicam have anti-tumor effects on gastric cancer, but the mechanism is still unclear yet.Objective The aim of this study was to investigate the regulative effects and its mechanism of ursolic acid and meloxicam on the proliferation and apoptosis in a human gastric cancer cell line, SGC-7901.Methods SGC-7901 cells were seeded in RPMI-1640 supplemented with 10% heat-inactivated fetal calf serum and routinely incubated for 24 h. After treatment with either ursolic acid or meloxicam both at a final concentration of 10, 20, 40 and 80μmol/L, thereafter cultured in serum-free medium for 12 h, 24 h and 48 h, the cell proliferation was determined by using methyl thiazolyl tetrazolium (MTT) colorimetric assay. Being treated with different concentrations of ursolic acid and meloxicam for 24 h, flow cytometric analysis (FCM) was used to detect the apoptosis. The expression of COX-2 was assessed by western blot analysis. The levels of prostaglandin E₂ (PGE₂) in the culture media were measured by enzyme-linked immunosorbent assay (ELISA).Results Both ursolic acid and meloxicam significantly inhibited SGC-7901 cell proliferation in a dose- and time-dependent manner. The 50% inhibitory concentrations (IC₅₀) for ursolic acid and meloxicam were 107.1±17.4 and 82.0±10.6μmol/L, 73.8±10.6 and 48.8±7.3μmol/L, 46.0±8.1 and 16.4±8.2μmol/L, at 12 h, 24 h and 48 h respectively. The inhibitory rate in the cells treated with ursolic acid was significantly lower than that with meloxicam (P < 0.05). The apoptosis rates were 4.7±0.4% and 5.9±0.5%, 6.4±0.5% and 7.5±0.6%, 9.9±1.8% and 13.4±2.3%, 14.5±1.7% and 21.9±2.5%, when SGC-7901 cell were treated with Ursolic acid and meloxicam for 24 h at 10, 20, 40, 80μmol/L respectively. Ursolic acid and meloxicam dose-dependently inhibited COX-2 expression and PGE2 synthesis in SGC-7901 cells. The inhibitory effect of ursolic acid on the expression of COX-2 and the synthesis of PGE2 were significantly lower than that of meloxicam (P < 0.05).Conclusion These results indicate that ursolic acid and meloxicam inhibit the proliferation of gastric cancer cells. Meanwhile, they also induced the apoptosis of SGC-7901 cell. This inhibition on cell proliferation and the induction of cell apoptosis may be mediated by down-regulating the expression of COX-2 and reducing the production of PGE2.