Inhibitory Effect And Molecular Mechanism Of Oleuropein On Gastric Cancer

Objective: To investigate the effects of natural compound oleuropein(Oleu)on the proliferation,cloning,migration,invasion and apoptosis of gastric cancer cells SGC-7901,and to further explore the regulation mechanism of Oleu on the growth of SGC-7901 cells,so as to provide new methods and ideas for the clinical application of Oleu.Methods: Normal gastric epithelial cell GES-1 and gastric cancer cell line SGC-7901 were used as experimental models.The effects of Oleu at different concentrations and at different time points on the proliferation of normal gastric mucosal epithelial cells GES-1 and gastric cancer cells SGC-7901 were detected by thiazolium blue(MTT)colorimetry.The plate clone formation experiment verified if Oleu could inhibit the clone formation of gastric cancer cell line SGC-7901.Wound healing experiment verified if Oleu could inhibit the lateral migration of gastric cancer SGC-7901 cells.Transwell migration and invasion assay was used to verify the effect of Oleu on the longitudinal migration and invasion ability of gastric cancer SGC-7901 cells.The Hochest 33342/PI double-staining apoptosis experiment confirmed that Oleu could promote the apoptosis of SGC-7901 cells.The total and phosphorylation levels of STAT3 protein in SGC-7901 cells and the expression of Bad,Bax,Bcl-2,Cleaved caspase-9,Cleaved caspase-3 apoptotic related proteins,cyclins p53 and CDK2 were detected by Western blot assay.Results: 1.Compared with normal gastric mucosa GES-1 cells,Oleu could significantly inhibit the proliferation of gastric cancer SGC-7901 cells in a time-concentration dependent manner.2.The plate clone formation assay,cell wound healing assay and Transwell migration and invasion assay showed that Oleu could dose-dependently inhibit the clone formation,migration and invasion of SGC-7901 cells.3.Hochest 33342/PI double-staining apoptosis assay showed that Oleu promoted the apoptosis of SGC-7901 cells in a concentration-dependent manner.4.Western blot results showed that Oleu promoted the activation of apoptosis in SGC-7901 cells,decreased the phosphorylation of STAT3,and up-regulated the apoptotic factors Bad,Bax,Cleaved caspase-9,Cleaved caspase-3,and down-regulated Bcl-2.The cyclin p53 was significantly up-regulated and CDK2 was significantly down-regulated in a concentration-dependent manner.Conclusions: Oleu can significantly inhibit the proliferation,clone formation,migration and invasion of SGC-7901 cells,and the mechanism may be related to the decrease of phosphorylation level of STAT3.The promotion of apoptosis by Oleu may be related to the up-regulation of Bad,Bax,Cleaved caspase-9,Cleaved caspase-3,down-regulation of Bcl-2,up-regulation of cyclin p53,and down-regulation of CDK2.