阿托伐他汀抑制肝癌细胞增殖作用的研究

Effects of Atorvastatin on Proliferation and Expression of COX-2 Protein in Hepatic Cancer Cells

目的:体外观察阿托伐他汀对人肝癌HepG2细胞增殖、细胞周期及COX-2蛋白表达的影响。方法:取对数期人肝癌HepG2细胞,加入阿托伐他汀使其终浓度为0、0.1、1、10和100μmol/L,采用细胞计数法及四甲基偶氮唑盐(MTT)法观察阿托伐他汀对HepG2细胞增殖的影响,流式细胞仪(FCM)研究阿托伐他汀对细胞周期的作用,免疫细胞化学观察阿托伐他汀对COX-2蛋白表达的影响。结果:体外阿托伐他汀呈浓度和时间依赖性地抑制HepG2细胞的增殖,但0.1μmol/L组与0 μmol/L组差异无统计学意义。细胞周期分析显示,阿托伐他汀作用24h后,呈浓度依赖性改变细胞周期分布,G0/G1期细胞的比例增高,S期及G2/M期的细胞比例降低,但细胞凋亡不明显。体外阿托伐他汀呈浓度依赖性地抑制HepG2细胞COX-2蛋白的表达。结论:体外阿托伐他汀对HepG2细胞增殖有抑制作用,该作用可能与使细胞生长阻滞于G0/G1期及抑制COX-2蛋白表达有关。

Objective： To investigate the effect of atorvastatin on the proliferation, cell cycle and COX -2 protein expression of human hepatocellular carcinoma （HepG2） cells in vitro. Methods： The human hepatocellular carcinoma HepG2 cells were employed during logarithmic growth phase and atorvastatin were added at the final concentrations of 0, 0.1, 1, 10 and 100 μmol/L respectively. The proliferation of the cells was detected by cell counting and MTT assay. The cell cycle was measured by flowcytometry （FCM）. The COX -2 protein expression was detected by immunocytochemistry. Results： Atorvastatin suppressed the growth of HepG2 cells in a concentration - and time -dependent manner, but there was no significant difference between 0.1 μmol/L group and 0 μmol/L group. The cell cycle analysis revealed that atorvastatin caused a concentration-dependent increase of cells in G0/G1 phase cell cycle. At the same time the cells in S and G2/M phase were decreased. However, apoptosis was not obvious in HepG2 cells. Atorvastatin inhibited COX -2 protein expression in a concentration-dependent manner. Conclusion： Atorvastatin inhibited HepG2 cell growth in vitro, which may be related to its inhibitory effect on COX-2 protein expression and arresting HepG2 cells at G0/G1 phase cell cycle.