HDACS抑制剂对人肝癌细胞株HepG2作用的研究  

STUDY OF THE EFFECT OF HDACS INHIBITOR——TRICHOSTATIN A ON HUMAN HEPATOCELLULAR CARCINOMA HEPG2 CELL LINE

作　　者：段承刚[1] 代永红 王丽[1] 刘晓燕[1] 梅志强[1] 何涛[1] 

机构地区：[1]泸州医学院医学基础研究中心,四川泸州646000 [2]重庆市江津区中心医院重症科

出　　处：《泸州医学院学报》2011年第3期244-247,共4页Journal of Luzhou Medical College

基　　金：四川省卫生厅科研项目(No.060065)

摘　　要：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)对人肝癌细胞株HepG2(以下简称HepG2)和正常肝细胞株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、脱氧核苷酸末端转移酶介导的dTP缺口末端标记技术(TUNEL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:(1)HepG2细胞经TSA处理后,电镜下超微结构发生了凋亡早期改变。(2)小剂量TSA(250nmol/L)对HepG2细胞具有较强的生长抑制作用,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。(3)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。To investigate the mechanism of trichostatin A （TSA） by comparing its effects on prolif- eration and apotosis of human hepatocellular carcinoma HepG2 cellline and normal hepatocellular LO2 cellline. Methods：MTY, Phase-contrast-microscopy, electron-microscopy, terminal deoxynucleotidyl transferase TdT-medi- ated dUTP-biotin nick end labeling （TUNEL）, and immunocytochemistry were conducted to observe the alteration of cell line proliferation, apotosis and apoptosis-related protein of HepG2 and LO2 after treated with TSA.Results：（1） The HepG2 cellline altered their cell line forms and the early apoptosis was observed under electron microscope. （2） Low dosage TSA （250nmol/L） had a very strong inhibition to HepG2 cellline, nearly with no effect on LO2 cellline. When the TSA concentration reached 1000nmol/L or above, apparent cytotoxicity appeared to LO2 cell line. （3）TSA can induce the apoptosis of HepG2 cell line and increase the expressions of Bax. Conclusion： TSA can inhibit the proliferation of HepG2 cell line. This may be related to cell apoptosis by upmodulating the expression of Bax.

关 键 词：肝癌 组蛋白去乙酰化酶 古抑菌素A 细胞凋亡 

分 类 号：R735.7[医药卫生—肿瘤] Q503[医药卫生—临床医学]