曲古抑菌素A对结肠癌细胞株SW480细胞周期影响的机制研究

Effect of Trichostatin A on Cell Cycle and the Expression of Cell Cycle-Associated Genes in Human Colon Cancer Cell Lines

为了研究组蛋白去乙酰化酶(HDACs)抑制剂曲古抑菌素A(TSA)对结肠癌细胞周期和凋亡的影响,初步探讨TSA作用细胞周期的可能机制,将人结肠癌细胞系SW480经TSA处理后,运用流式细胞术检测细胞周期、凋亡以及细胞周期素的变化,最后采用western-blot对细胞周期相关的基因进行检测.结果表明,TSA处理细胞后,TSA能够延缓细胞周期G1-S进程,阻滞细胞于G1期,并且影响细胞周期素cyclinE、cyclinA聚集,而对凋亡无明显的影响.Western-blot显示,TSA能够上调p21Waf1/Cip1、p27Kip1的表达,下调CDK2、cyclinE以及cycli-nA的表达.以上结果说明在结肠癌细胞中,TSA能够通过上调p21Waf1/Cip1、p27Kip1的表达以及下调CDK2、cy-clinE、cyclinA的表达,从而阻滞细胞周期于G1期,最终影响肿瘤细胞的生长,以上研究为HDAC抑制剂应用于结肠癌治疗提供了理论依据.

To investigate the effects of the histone deacetylase inhibitor, trichostain A（TSA）, on cell cycle and apoptosis in human colon cancer cell lines. The colon cancer cell lines （SW480） was treated with the histone deacetylase （HDAC） inhibitor, trichostatin A （TSA） and the cell cycle distribution was studied by flow cytometry （FCM） . The expression of p21^Waf1/Cip1、p27^Kip1, CDK2, CyclinE and CyclinA were detected by west- era-blot. The results indicated that TSA delayed cell cycle Gt-S progression and inhibited accumulating of cyclinE, cyclinA. No obvious changes were observed in apoptosis after TSA treatment. The expression of p21^Waf1/Cip1、p27^Kip1 was markly increased and the expression of CDK2, CyclinE, CyclinA was down-regulated after treated with TSA. It could be concluded that in human colon cancer cell line, HDAC inhibitor, TSA in- duced a Gt cell cycle arrest and have effect on cell proliferation through stimulating the p21^Waf1/Cip1、p27^Kip1 gene expression and blocking the CDK2, CyclinE, CyclinA expression. Theoretic proof was provided for clinical treatment by histone deacetylase inhibitor in human colon cancer.