BEZ235对体外前列腺癌细胞的抑制作用

摘要

Objective:To determine effects of BEZ235,an inhibitor of phosphoionsitol-3-kinase (PI3K)/ mTOR,on the cell proliferation and migration in human prostate carcinoma lines including RWPE-1,PC3,and DU 145 cells.Methods:Viability of RWPE-1,PC3,and DU145 cells was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay,while cell migration was analyzed by wound healing assay.Western blot and immunofluorescence were used to examine the changes of relevant protein expression.Results:The proliferation of PC3 and DU145 cells was effectively inhibited by BEZ235 (P<0.01),whereas RWPE-1 was not obviously inhibited.Invasion and migration of PC3 and DU145 cells were attenuated by BEZ235 via EMT pathway.Conclusion:The PI3K/mTOR dual inhibitor BEZ235 shows substantial anti-tumor activity in human prostate carcinoma lines of PC3 and DU145 cells,which may be involved in the EMT pathway.%目的:探讨PI3K/mTOR双重靶向抑制剂BEZ235对人前列腺癌细胞株的增殖、迁移能力的影响.方法:采用MTT实验分析BEZ235对正常前列腺上皮细胞RWPE-1和前列腺癌细胞PC3及DU145增殖能力的影响;划痕试验检测BEZ235对RWPE-1,PC3及DU145细胞迁移的影响;Western印迹及免疫荧光染色方法检测BEZ235对上皮-间质转化(epithelial-mesenchymal transition,EMT)相关标志物蛋白表达的影响.结果:BEZ235对PC3和DU145细胞的增殖具有明显的抑制作用(P<0.01),而对RWPE-1作用不明显;BEZ235明显上调PC3和DU145细胞标志物E-cadherin的表达,下调间质标志物Vimentin的表达(P<0.01).结论:BEZ235可体外抑制PC3和DU145细胞增殖和迁移,其部分机制可能是通过抑制EMT途径而实现.