抑制Akt通路对前列腺癌细胞株糖酵解影响的探讨  

Effects of Akt Signaling Inhibition on Cellular Glycolysis in Prostate Cancer Cell Lines

作　　者：徐莲[1] 王恩成[1] 孙晓光[1] 黄钢[1] 

机构地区：[1]上海交通大学医学院附属仁济医院核医学科,200127

出　　处：《放射免疫学杂志》2011年第2期153-156,共4页Journal of Radioimmanology

基　　金：国家自然基金重点项目(30830038);上海市重点学科第三期(S30203)

摘　　要：目的:探讨LY294002和氯化钴对PC3和DU145细胞糖酵解的影响及可能的机制。方法:不同浓度的LY294002、氯化钴和LY294002联合氯化钴处理PC3和DU145细胞,检测细胞的葡萄糖消耗、Akt的磷酸化、HIF-1α的蛋白表达和几个基因的mRNA表达。结果:LY294002减少PC3细胞Akt的磷酸化、HIF-1α的蛋白表达和LDH1及其他几个基因的mRNA表达,明显降低PC3细胞的葡萄糖消耗,对DU145细胞的葡萄糖消耗降低得较少。氯化钴增加PC3和DU145细胞HIF-1α的蛋白表达,升高细胞的葡萄糖消耗。与单独的LY294002相比,LY294002联合氯化钴回升细胞的葡萄糖消耗、HIF-1α的蛋白表达和几个基因的mRNA表达。结论:LY294002通过抑制Akt的磷酸化降低细胞的葡萄糖消耗,氯化钴通过诱导HIF-1α的蛋白表达升高细胞的葡萄糖消耗,Akt磷酸化抑制引起的葡萄糖消耗降低是部分由HIF-1α介导的。Objective To investigate the effects of LY294002 and CoCl2 on cellular glycolysis in prostate cancer cell lines PC3 and DU145 and the probable mechanisms.Methods PC3 and DU145 cells were treated with different concentrations of LY294002,CoCl2 and LY294002 combined with CoCl2,cellular glucose consumption,phosphorylation of Akt,protein expression of HIF-1α,mRNA expression of several enzymes in celluar glycolysis were measured.Results LY294002 inhibited the phosphorylation of Akt,reduced the protein expression of HIF-1α and the mRNA expression of LDH1 and several other enzymes in celluar glycolysis,and decreased the glucose consumption in PC3 cells,but glucose consumption was less decreased in DU145 cells.CoCl2 induced the protein expression of HIF-1α,and increased the glucose consumption in PC3 and DU145 cells.Compared with LY294002,LY294002 combined with CoCl2 increased the glucose consumption,induced the protein expression of HIF-1α and the mRNA expression of several enzymes in celluar glycolysis.Conclusion LY294002 decreased the glucose consumption by inhibiting the phosphorylation of Akt,CoCl2 increased the glucose consumption by inducing the protein expression of HIF-1α,and the decrease of glucose consumption caused by inhibiting the phosphorylation of Akt was partial mediated by HIF-1α.

关 键 词：葡萄糖消耗 AKT通路 缺氧诱导因子-1Α 前列腺癌细胞株 

分 类 号：R737.25[医药卫生—肿瘤]