MS-275抑制肝癌细胞HepG2增殖及其相关信号传导机制的体外实验研究

目的研究组蛋白去乙酰化酶(HDAC)抑制剂MS-275诱导人肝癌细胞株HepG2细胞周期阻滞作用,并对其信号传导机制进行初步探讨。方法体外培养人肝癌细胞株HepG2;应用MTT比色法观察MS-275对HepG2的生长抑制作用,应用流式细胞仪检测MS-275对细胞周期的影响;Western印迹分析细胞周期蛋白(Cyclin)D1、p21、p-p38MAPK三种蛋白表达的差异。结果HDAC抑制剂MS-275能抑制肝癌细胞生长,具有时间和剂量的依赖性。可以引起细胞周期G0-G1期阻滞。MS-275可以使HepG2细胞p21蛋白表达提高,CyclinD1蛋白表达降低,在SB203580组两蛋白的表达又恢复到对照组水平。p-p38MAPK蛋白在两组表达均提高。结论MS-275能诱导肝癌细胞株的细胞周期阻滞,这种作用可能是通过p38MAPK信号传导途径介导的,与下调CyclinD1的表达、上调p21的表达有关。

Suppression of HepG2 proliferation induced by MS-275 and its related signal transduction mechanism in vitro

Objective To investigate the influence of histone deacetylase (HDAC) inhibitor MS-275 induced cell cycle stasis in human hepatoma cell line HepG2,and approach their signal transduction mechanism.Methods HepG2 cells were cultured in vitro.Inhibition of proliferation on growth of HepG2 by MS-275 was measured by MTT assay.Flow cytometry (FCM) was used to examine the effect s of MS-275 on the cell cycle of HEPG2 cells.The differences in the expressions of p38MAPK,Cyclin D1 and p21 protein were estimated by Western blot.Results HDAC inhibitor MS-275 inhibited HepG2 cells growth and caused G0-G1 arrest with time and dose dependent.MS-275 increased p21 protein levels and decreased Cyclin D1 protein levels.In SB203580 group the levels of two protein reverted to the levels of the control group.The level of p-p38MAPK protein was increased in two groups.Conclusions MS-275 can induce cell cycle stasis of HepG2,which might be mediated by p38MAPK signal transduction pathway and associated with down-regulating the expression of Cyclin D1 protein and up-regulating the expression of p21 protein.