Effects of Ursolic Acid on Cell Apoptosis in PC-3 Cells and Its Mechanisms

Objective:To explore the effect of Ursolic acid on cell apoptosis in PC-3 cells and discuss its possible mechanisms. Methods:PC-3 cells were cultured in vitro. After treatment by Ursolic acid at different concentrations respectively at different time points,the cell survival was determined by the MTT method. The changes of cell morphology were observed by inverted microscope. Apoptosis was detected by flow cytometry. The relative activity of Caspase-3 and Caspase-9 was monitored by spectrophotometer. The changes of protein expression of COX-2 and PTEN were detected by western blot. Results:From the data of MTT,the cell proliferation of PC-3 cells was inhibited by Ursolic acid in a dose-dependent and timedependent manner. Typical apoptosis morphology of PC-3 cells was observed by inverted microscope. Flow cytometry assays showed that Ursolic acid significantly induced apoptosis in PC-3 cells. After treated with Ursolic acid,the apoptosis rate of PC-3 cells was 12.5%,23.3%,and 35.4% respectively,which showed an obvious concentration-effect relationship. The relative activity of Caspase-3 of Ursolic acid group was 0.194±0.02,0.253±0.04 and 0.316±0.03 respectively. And the relative activity of Caspase-9 was 0.177±0.02,0.234±0.03 and 0.305±0.04. The data of western blot showed that Ursolic acid down-regulated COX-2 and up-regulated PTEN in a dose-dependent manner. Conclusion:Ursolic acid can inhibit the proliferation of PC-3 cells and induce apoptosis,and the mechanism of Ursolic acid on apoptosis may be related to the down regulation of COX-2 expression and up regulation of PTEN expression,as well as the increase of relative activity of Caspase-3 and Caspase-9. Ursolic acid may be a promising anti-tumor agent for mammary cancer treatment.