古抑菌素对人肝癌细胞作用的研究

Study of effect of TSA on human hepatocellular carcinoma cells

目的:通过组蛋白去乙酰化酶(histone deacetylase,HDACS)抑制剂古抑菌素A(Trichostatin A,TSA)对人肝癌细胞HepG2(以下简称HepG2)和正常肝细胞LO2(以下简称LO2)增殖与凋亡作用的比较,探讨TSA对肝癌的作用机制。方法:应用光学显微镜、透射电镜、四氮唑蓝(MTT)法、免疫细胞化学法观察经不同浓度TSA处理后的HepG2和LO2的增殖、凋亡与凋亡相关蛋白的改变。结果:HepG2细胞经TSA处理后,电镜下超微结构发生了凋亡早期改变;小剂量TSA对HepG2细胞具有较强的抑制作用,对LO2细胞影响不明显,当TSA浓度达到1000nmol/L以上时,对LO2表现出明显的细胞毒性作用;TSA可诱导HepG2细胞凋亡,并增加凋亡相关蛋白Bax的表达。结论:TSA可明显抑制肝癌细胞HepG2的增殖,其机制可能与上调Bax的表达,诱导细胞凋亡有关。

Objective：To investigate the mechanism of trichostatin A （TSA） by comparing the effects of TSA on the proliferation and apotosis of human hepatocellular carcinoma HepG2 cells and normal hepatocellular LO2 cells. Methods：MTT,phase-contrast-microscope,electron-microscopy, immunocytochemistry were conducted to observe the alteration of cell proliferation, apotosis and apoptosis-related protein of HepG2 and L02 after treated with TSA.Results：The HepG2 ceils altered in their cells forms and the early apoptosis was observed under electron microscope. Low dosage TSA had a very strong inhibition to HepG2 cells, nearly no efficacy on LO2 cells. When the TSA concentration of 1000nmol/L or above,the apparent cytotoxicity appeared to LO2 cells. TSA could induce the apoptosis of HepG2 cells and increase the expressions of bax. Conclusion：TSA can inhibit the proliferation of HepG2 cells. This maybe related to cell apoptosis by upmodulating the expression of Bax.