罗格列酮对HT29、HCT116结肠癌细胞凋亡影响及机制探究

Rosiglitazone promotes apoptosis in colon cancer HT29 and HCT116 cells through AKT/GSK3β signalling pathway

目的探讨罗格列酮对结肠癌HT29、HCT116细胞增殖、凋亡情况的影响以及AKT/GSK3β信号通路的变化。方法 HT29、HCT116结肠癌细胞经不同浓度罗格列酮(20.0μmol/L,40.0μmol/L,80.0μmol/L)处理后,采用MTT法检测细胞增殖能力的变化,annexin-V FITC/PI试剂盒检测细胞凋亡情况,Western blot检测Bcl2、Bax以及Akt、GSK3β表达情况。结果与空白对照组相比,不同浓度的罗格列酮对HT29、HCT116结肠癌细胞的增殖均有影响(P<0.01),并且影响呈剂量依赖关系;不同浓度的罗格列酮对HT29、HCT116细胞均有诱导凋亡的作用(P<0.01),且诱导HT29、HCT116细胞凋亡呈剂量依赖性;罗格列酮处理细胞48 h后,与空白对照组相比Bcl2/Bax表达水平、P-GSK3β、P-Akt表达水平明显下降(P<0.01),Akt、GSK3β表达水平较空白对照组差异无显著性(P>0.05)。结论罗格列酮可能通过抑制Akt/GSK3β通路的激活,改变Bcl2/Bax情况,发挥抑制细胞增殖、诱导凋亡的作用。

Objective To investigate the effect of rosiglitazone on the proliferation and apoptosis of colon cancer cells and the changes in the AKT/GSK3β signaling pathway. Methods Different concentrations of rosiglitazone（ 20. 0μmol/L,40. 0 μmol/L,80. 0 μmol/L） were used to treat colon cancer HT29 cells and HCT116 cells. Cell proliferation was detected by MTT assay. Annexin V FITC/PI cell death detection kit was used to test the cell apoptosis rate. The expression of apoptotic protein Bcl-2, Bax and Akt, GSK3β were detected by Western blot. Results Different concentrations of rosiglitazone had different effect on the proliferation of colon cancer cells compared with the blank control group,and showed a dose dependence（ P〈 0. 01）. With the increase of rosiglitazone dose,the apoptosis-inducing effectwas increased dose-dependently（ P〈 0. 01）. When the cells were treated with rosiglitazone for 48 h,the expressions of Bcl-2/Bax,p-GSK3β,and p-Akt were significantly decreased compared with the blank control group（ P〈 0. 01）,but the expression level of Akt and GSK3β was not significantly different compared with the blank control group（ P〈 0. 05）.Conclusions Rosiglitazone significantly induces apoptosis and inhibits the proliferation of HT29 cells. It may be via inhibiting Akt/GSK3β signaling pathway and change the ratio of Bcl-2/Bax.