丙戊酸钠对肝癌SMMC-7721细胞增殖和细胞周期的影响及机制

目的:探讨丙戊酸钠(VPA)对人肝癌SMMC-7721细胞增殖、细胞周期及对p21WAF1/CIP1mRNA表达的影响.方法:实验分为空白对照组、PBS组、VPA0.2mmol/L组、VPA1.0mmol/L组和VPA5.0mmol/L组.不同浓度VPA干预人肝癌SMMC-7721细胞24h、48h和72h,采用MTT法检测细胞存活率,流式细胞仪检测细胞周期;干预72h后,用Real-timePCR法检测VPA干预72h后p21WAF1/CIP1mRNA的表达情况.结果:与空白对照组及PBS组比较,不同浓度的VPA作用24h,48h及72h时组肝癌SMMC-7721细胞增殖均出现了不同程度抑制(请将具体数据列出来P<0.05),随着VPA药物浓度升高,细胞增殖抑制作用逐渐增强,随作用时间延长,抑制程度逐渐增强(P<0.05).随药物浓度升高,G1期细胞比例逐渐增多,S期细胞比例逐渐减少,细胞发生G0/G1期阻滞.VPA干预肝癌SMMC-7721细胞72h后,VPA组p21WAF/CIP1mRNA表达较空白对照组及PBS组表达明显升高(请将具体数据列出来P<0.01).结论:VPA可抑制人肝癌SMMC-7721细胞的增殖,且呈时间及剂量依赖性,并诱导出现G0/G1细胞周期阻滞,同时上调p21WAF1/CIP1mRNA的表达.

Effect of valproic acid on cell proliferation and cell cycle progression in human hepatoma cell line SMMC-7721

AIM:To investigate the effect of valproic acid(VPA)on cell proliferation,cell cycle progression and expression of p21WAF1/CIP1 mRNA in human hepatoma cell line SMMC-7721 in vitro.METHODS:SMMC-7721 cells were treated with different concentrations(0.2,1.0 and 5.0 mmol/L)of VPA for different durations(24,48 and 72 h).Cell growth was measured by MTT assay.Cell cycle analysis was performed by flow cy-tometry.The expression of p21WAF1/CIP1 mRNA in SMMC-7721 cells treated with VPA for 72 h was detected by RT-PCR.RESULTS:Compared to the control group and PBS group,treatment with different concentrations of VPA for different durations significantly reduced cell growth to a varying extent(all P< 0.05).VPA administration suppressed cell proliferation in a time-and dose-dependent manner.After treatment with VPA,the percentage of cells in G 1 phase increased significantly and that of cells in S phase decreased,suggesting an arrest in G 0 /G 1 phrase.Significant up-regulation of p21WAF1/CIP1 mRNA was observed in SMMC7721 cells 72 h after treatment with VPA.CONCLUSION:VPA could significantly suppress cell proliferation in a time-and dose-dependent manner,and result in a cell cycle arrest in G 0 /G 1 phase by inducing elevated expression of p21WAF1/CIP1 mRNA in SMMC-7721 cells.