Flavopiridol通过调节CDK4/CDK6/cyclinD1复合物表达抑制肝癌细胞增殖

目的研究flavopiridol对肝癌细胞Huh7增殖、凋亡和细胞周期的影响。方法Flavopiridol处理Huh7细胞后，检测细胞增殖和凋亡，进行细胞周期分析。Westernblot检测flavopiridol对cDK4／cDK6／cyclinD1复合物表达的影响。结果Flavopiridol可显著抑制Huh7细胞增殖；Flavopiridol可剂量依赖性导致Huh7细胞发生凋亡，空白对照组凋亡细胞2．65％，550nmol／L剂量处理组凋亡细胞14．17％；Flavopiridol可剂量依赖性引起Huh7细胞G1期阻滞，空白对照组G1期细胞51．06％，550nmol／L剂量处理组G1期细胞57．53％；Flavopiridol可抑制Huh7细胞Gl期相关的蛋白细胞周期素依赖激酶（CDK）4，CDK6，细胞周期素D1（cyclinD1）的表达。结论Flavopiridol通过抑制肝癌细胞G1期cDK4／cDK6／cyclinD1蛋白复合物表达，引起细胞G1期阻滞并发生凋亡，从而抑制细胞增殖。

Flavopiridol inhibit hepatocellular carcinoma cell proliferation via regulating expression of CDK4/CDK6/cyclinD1 complex

Objective To investigate the effects of flavopiridol on growth, cell apoptosis, and cell cycle of hepatocellular carcinoma cell（HCC） Huh7. Methods Huh7 cells were treated with flavopiridol, then cell proliferation, cell apoptosis and cell cycle were assessed. Protein expression of CDK4/CDK6/cyclinD1 complex was determined by western blot. Results Flavopiridol inhibited Huh7 cell growth. Flavopiridol induced dose-dependent cell apoptosis in Huh7 cells. Percentage of apoptotic cells increased from 2.65% in control cells to 14.17% in flavopiridol treating（550nmol/L） cells. Flavopiridol significantly blocked Huh7 cell cycle at G1 phase and percentages of cell arrested at G1 phase increased from 51.06% in control cells to 57.53% in ceils treated with 550 nmol/L of flavopiridol. Flavopiridol can inhibit protein expressions of CDK4, CDK6 and cyclinD1 in Huh7 cells. Conclusion Flavopiridol inhibits cell proliferation through regulating expressions of G1 phase protein complex CDK4/CDK6/cyclinD1, which lead to G1 phase arrest and apoptosis in HCC cells.