组蛋白去乙酰化酶2表达下调对宫颈癌细胞增殖和细胞周期的影响

Effect of down-regulation of histone deacetylase 2 protein expression on cell proliferation and cell cycle in cervical carcinoma

目的探讨组蛋白去乙酰化酶2（HDAC2）表达下调对宫颈癌细胞增殖和细胞周期的影响，并分析其可能的分子机制。方法将HI）AC2小干扰RNA（siRNA）和对照siRNA转染宫颈癌HeLa细胞，采用细胞增殖与活性检测试剂盒（CCK-8）分析转染前后细胞增殖的变化，利用流式细胞术检测转染前后细胞周期分布的变化，采用Westernblot方法分析与细胞增殖和细胞周期相关蛋白表达的变化。结果HDAC2 siRNA能明显下调宫颈癌细胞中HDAC2蛋白的表达，其表达下调能明显抑制宫颈癌细胞的增殖。HDAC2 siRNA组中HeLa细胞在G0／G1期的细胞比率为63．3％±2．0％，显著高于未处理组（29．3％±1．7％）和对照siRNA组（29．4％±1．7％），F=354．181，P=0．000。Westernblot结果显示，HDAC2表达下调能明显抑制cyclin D1、cyclin E和CDK2蛋白的表达，增加p21蛋白的表达。结论HDAC2表达下调介导的细胞增殖抑制和周期阻滞可能与cyclin D1、cyclin E和CDK2蛋白表达的下调和p21蛋白表达的升高密切相关。

Objective To study the effect of down-regulation of histone deacetylase 2 （HDAC2） expression on cell proliferation and cell cycle in cervical carcinoma cell lines HeLa. Methods HDAC2 siRNA and control siRNA were transfected to HeLa cells. CCK-8 and flow cytometry were used to analyze the changes of cell proliferation and cell cycle, respectively. Western blot was employed to detect the changes of cell proliferation and cell cycle-related proteins. Results HDAC2 siRNA significantly down-regulated the expression of HDAC2 protein in HeLa cells, resulting in marked inhibition of cell proliferation. In addition, the percentage of cells in G0/G1 phase in HDAC2 siRNA group （63.3% ± 2.0% ） was significantly higher than that in untreated group （29.3% ±1.7% ） or control siRNA group （29.4% ±1.7% ） ,F = 354. 181, P = 0. 000. Furthermore, Western blot demonstrated that down-regulation of HDAC2 expression decreased the expression of cyclin D1, cyclin E and CDK2 proteins but increased the expression of p21 protein. Conclusions Down-regulation of HDAC2 expression mediates proliferation inhibition and cell cycle arrest. It is associated with decrease in eyelin D1, cyclin E and CDK2 protein expression and increase in p21 protein expression.