罗格列酮对肝癌细胞SMMC-7721增殖、凋亡及PTEN、存活蛋白表达的作用

Effects of rosiglitazone on proliferation,apoptosis and expression of PTEN and survivin in liver cancer cell line SMMC-7721

目的:探讨过氧化物酶体增殖激活物受体γ(peroxisome proliferators-activated receptorγ,PPARγ)配体罗格列酮对人肝癌细胞SMMC-7721增殖、凋亡及肿瘤抑制基因PTEN和存活蛋白(survivin)表达的影响。方法:经不同浓度罗格列酮(0、0.1、1、10和100μmol/L)处理SMMC-7721细胞24、48和72 h后,用MTT法测定细胞的增殖情况,FCM法检测细胞周期变化和凋亡情况,Western印迹法检测细胞中PTEN和survivin蛋白表达的变化。结果:罗格列酮可以显著抑制SMMC-7721细胞增殖(P<0.01);可使SMMC-7721细胞G0/G1期比例明显升高(P<0.05),G2/M期比值降低(P<0.05),并能显著诱导细胞凋亡(P<0.05),呈时间依赖性和剂量依赖性。罗格列酮能上调细胞PTEN的表达,并呈时间和剂量依赖性,而对survivin的表达则无明显改变(P>0.05)。结论:PPARγ被罗格列酮活化后可抑制SMMC-7721细胞增殖、诱导细胞凋亡,该作用可能是与上调细胞PTEN的表达有关。

Objective：To investigate the effects of peroxisome proliferators-activated receptor γ（PPARγ） ligand rosiglitazone on proliferations, apoptoses and expressions of PTEN and survivin in hepatocellular carcinoma cell line SMMC-7721 in vitro. Methods： After treatment with different concentrations of rosiglitazone （0, 0.1, 1, 10, and 100 μmol/L） for different periods （24, 48, 72 h）, the proliferation of SMMC-7721 cells were analyzed by MTT method. The cell cycle and apoptosis were detected by flow cytometry and the expressions of PTEN and survivin were detected by Western blotting. Results： Rosiglitazone significantly inhibited cell proliferation, increased the proportion of cells in G0/G1 phase, decreased the cell number in G2/M phase （P 〈 0.01, P 〈 0.05, P 〈 0.05） , and induced apoptosis of SMMC-7721 cells. The effects were in a time- and dose-dependent manners. Rosiglitazone up-regulated the expression of PTEN in a time-and dose-dependent manners. But it had no influence on expression of survivin. Conclusion ： The results in this study suggest that activation of PPARγ by its ligand rosiglitazone inhibits the proliferation and induced apoptosis of hepatoma cells, which may be through the up-regulation of PTEN expression.