曲古抑菌素A对人肝癌细胞HepG2中FHIT基因表达的影响  

Effect of TSA on the expression of FHIT in the human hepatoma cell line HepG2

作　　者：王丽[1] 刘晓燕[1] 龚舒[1] 何涛[1] 段承刚[1] 

机构地区：[1]泸州医学院医学分子生物学实验室,四川646000

出　　处：《重庆医学》2010年第15期1954-1956,共3页Chongqing medicine

基　　金：四川省卫生厅科研项目(060065)

摘　　要：目的研究组蛋白去乙酰化酶抑制剂——曲古抑菌素A(TSA)对人肝癌细胞HepG2中脆性组氨酸三联体(FHIT)基因表达的影响。方法以人肝癌细胞HepG2(简称HepG2)和正常肝细胞LO2(简称LO2)为实验对象,每种细胞设为对照组和不同浓度TSA(125、250、500、1000、2000nmol/L)处理组,于倒置显微镜下观察细胞形态变化,MTT比色法测定TSA对两种细胞增殖抑制情况,RT-PCR检测FHIT基因表达,Western blot检测FHIT蛋白表达。结果经TSA处理的HepG2细胞增殖速度明显减慢;不同浓度TSA对HepG2细胞的增殖均有抑制作用,并有明显的剂量依赖和时间依赖关系,对LO2的抑制作用不明显(P>0.05);HepG2中FHIT mRNA表达和蛋白表达均增强,差异有统计学意义(P<0.05)。结论 FHIT基因的异常改变可能与组蛋白异常去乙酰化有关,TSA可通过抑制去乙酰化酶活性,上调FHIT基因表达而抑制肝癌细胞增殖。Objective To investigate the effect of TSA on the expression of fragile histidine triad（FHIT） in the human hepatoma cell line HepG2. Methods After the human hepatoeareinoma cells and the normal liver cells had been treated with various concentrations of TSA in different duration in vitro,cell morphologies were observed by the inverted light microscope, and cell viability were analyzed by MTT assay. The expression of FHIT was analyzed by RT-PCR and Western blot. Results TSA inhibited the proliferation of HepG2 cells in dose-dependent and time-dependent manners,but the normal liver cell line LO2 was not sensitive to the TSA. The expression of FH1T mRNA and FHIT protein were increased after treatment of TSA（P〈0.05）. Conclusion The alternation of FHIT gene correlated with abnormal histone deacetylation and TSA could inhibit the proliferation of the hepatocarcinoma cell line HepG2, which were associated with inhibition of enzymatic activity of HDACS, regulation of FHIT gene transcription and FHIT protein expression.

关 键 词：脆性组氨酸三联体 曲古抑菌素A 肝癌 人肝癌细胞HEPG2 

分 类 号：R735.7[医药卫生—肿瘤] R730.54[医药卫生—临床医学]