TSA对不同肝癌细胞株增殖和凋亡的作用及其对HBV复制的影响  

Effects of trichostatin A(TSA) on the proliferation and apoptosis of hepatoma cell lines and the the replication of hepatitis B virus(HBV)

作　　者：谢静[1] 王锋[2] 梅浙川[1] 唐开福[3] 任红[3] 

机构地区：[1]重庆医科大学附属第二医院消化内科,重庆400010 [2]四川省华蓥市人民医院,四川638600 [3]重庆医科大学病毒性肝炎研究所,重庆400010

出　　处：《重庆医科大学学报》2008年第9期1025-1028,共4页Journal of Chongqing Medical University

基　　金：国家自然科学基金(30700708和30671869)资助

摘　　要：目的:比较组蛋白去乙酰化酶(Histone deacetylase,HDAC)抑制剂HDAC曲古抑菌素A(Trichostain A,TSA)对不同肝癌细胞株和正常肝细胞株增殖和凋亡的作用。初步研究TSA对HBV复制的影响。方法:应用四氮唑蓝(MTT)法,DNA琼脂糖凝胶电泳检测经不同浓度TSA处理过的3种肝癌细胞株HepG2、QGY7701、HepG2.2.15和正常肝细胞株L02,观察细胞增殖和凋亡的改变。用微离子酶联免疫法检测TSA处理组和对照组HepG2.2.15细胞上清中HBsAg和HBeAg的含量,实时荧光定量PCR检测细胞上清中HBV DNA含量,初步探讨TSA对HBV复制的影响。结果:TSA在一定浓度范围内能明显抑制不同肝癌细胞株的增殖,呈剂量依赖关系。对正常肝细胞株L02的增殖无明显影响。DNA凝胶电泳结果显示:在TSA处理组的3种肝癌细胞株HepG2、QGY7701、HepG2.2.15中可观察到细胞凋亡特异的DNA梯形带,然而,在对照组及正常肝细胞株中未见DNA梯形带。经TSA处理后的HepG2.2.15细胞上清中HBsAg、HBeAg及HBV DNA的含量均高于对照组1倍以上(P<0.05)。结论:组蛋白去乙酰化酶抑制剂TSA虽然可抑制肝癌细胞增殖并诱导凋亡,但是,TSA刺激HBV的复制。因此,对HBV阳性的肝癌患者,应尽量避免使用TSA。Objective：To compare the effect of histone deacetylase inhititor trichostatin A（TSA） on the proliferation and apotosis of different hepatoma cell lines and to investigate the effect of TSA on hepatitis B virus（HBV） replication. Methods：Human hepatoma cell lines HepG2,HepG2.2.15,QGY7701 and normal liver cell line L02 were treated with TSA, the effects on proliferation and apoptosis were examined by MTF assay and agarose gel electrophoresis of DNA; The viral proteins of hepatitis B surface antigen（HBsAg）and e antigen（HBeAg） in culture medium were measured using the Abbott Microparticle Enzyme Immunoassay kits;The medinm HBV DNA levels were quantified using HBV real-time PCR kit. Results： （a）TSA treatment repressed proliferation and induced apoptosis in hepatoma cell lines; （b）The normal repressed proliferation and induced apoptosis in hepatoma cell lines： （b） The normal liver cell line L02 was not sensitive to the treatment of TSA; （c）TSA stimulated HBV replication. Conclusions：TSA treatment could inhibit proliferation of different hepatoma lines,and the normal liver cell line L02 is not sensitive to TSA treatment. However,TSA stimulates HBV replication. Therefore,our results suggest that TSA might be a good chemotherapic candidate for hepatocellular carcinoma patients without HBV infection but may not be snited to treat hepatocellular cancer patients with HBV infection.

关 键 词：曲古抑菌素A 肝癌细胞株 增殖 凋亡 HBV 

分 类 号：R735.7[医药卫生—肿瘤]