FK228对人肝癌细胞HepG2凋亡及细胞周期基因表达的影响

目的：探讨FK228对人肝癌细胞HepG2凋亡及细胞周期基因p 21,cdk4表达的影响。方法：培养HepG2,应用四氮唑蓝(MTT)比色法观察FK228对HepG2的生长抑制作用,琼脂糖凝胶电泳分析细胞DNA特征,流式细胞术分析细胞周期,以RT-PCR检测HepG2细胞中p 21,cdk4基因表达水平。结果：组蛋白去乙酰化酶抑制剂FK228能抑制人肝癌细胞HepG2生长,并具有时间和剂量依赖性；FK228引起细胞周期G1期阻滞并诱导凋亡；FK228能明显促进p21mRNA转录,同时抑制cdk4mRNA的转录。结论：FK288能抑制HepG_2细胞增殖,诱导HepG_2细胞凋亡和周期阻滞；调节p21和cdk4基因的表达可能是FK228抑制HepG_2细胞生长的重要机制。

Effects of FK228 on cell apoptosis and expression of cell cycle gene in human hepatoma cell line HepG2

AIM:To investigate the effects of FK228,a novel histone deacetylase inhibitor on cell apopto- sis and expression of cell cycle gene p21 and cdk4 in human hepatoma cell line HepG2.METHODS:Inhibi- tion of proliferation on growth of HepG2 by FK228 was measured by MTT assay.DNA fragmentation was visual- ized by agarose gel electrophoresis;cell cycle arrest was detected by flow cytometry.The p21 and cdk4 mRNA expression of HepG2 was detected by RT-PCR.RESULTS:FK228 not only inhibited HepG2 growth with time and dose dependent but also induced apoptosis and blocked cell cycle progression in the G1 phase.RT-PCR demonstrated that FK228 significantly increased the expression of p21 mRNA and inhibited the expression of cdk4 mRNA simultaneously,which caused cell cycle arrest and apoptosis.CONCLUSION:FK228 treatment could inhibit proliferation of HepG2 with time and dose dependent,induce apoptosis and cell cycle arrest.The modulation of p21 and cdk4 genes may be critical for the marked antitumor activity of FK228 in vitro.