COX-2在乙肝病毒X蛋白(HBx)促进肝癌细胞和肝细胞增殖中的作用  

Effect of COX-2 on Proliferation of Hepatoma and Liver Cells Mediated by Hepatitis B Virus X Protein

作　　者：徐付卿[1] 山长亮[1] 叶丽虹[1] 张晓东[1] 

机构地区：[1]南开大学生命科学学院,教育部生物活性材料重点实验室,天津300071

出　　处：《中国生物化学与分子生物学报》2008年第10期968-973,共6页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家自然科学基金资助项目(No.30670959)~~

摘　　要：乙型肝炎病毒(hepatitis B virus,HBV)X蛋白(HBx)对肝癌的发生发展具有十分重要的作用.大量研究结果表明,与花生四烯酸代谢相关的磷脂酶COX-2与肿瘤细胞的增殖密切相关.为了阐明COX-2在HBx促进肝细胞增殖中的作用,在前期应用基因芯片方法检测发现稳定转染HBx基因的肝癌细胞H7402-X中COX-2基因表达明显上调的基础上,本研究应用免疫印迹技术在蛋白表达水平上获得了相同的结果.进而,应用COX-2的特异性抑制剂Indo分别作用H7402-X细胞和L-O2-X细胞(稳定转染HBx基因的人永生化L-O2肝细胞),观察HBx蛋白是否通过COX-2促进肝癌细胞或肝细胞增殖.BrdU掺入实验和流式细胞仪检测结果显示,50μmol/L的Indo可明显抑制H7402-X细胞和L-O2-X细胞的增殖.本研究结果提示,HBx可通过COX-2所介导的花生四烯酸代谢促进肝癌细胞和肝细胞增殖.Infection of hepatitis B virus （HBV） X protein （HBx） causes the development of hepatocellular carcinoma （HCC）. Many reports showed that cyclooxygenase （COX-2） involved in arachidonic acid metabolism is closely related to the proliferation of tumor cells. In order to reveal the effect of COX-2 on promoting liver cell proliferation meditaed by HBx, based on our previous finding that COX-2 was up-regulated by microarray assay in H7402-X cells stably transfected with HBx gene, we obtained the consistent result by Western blot analysis at protein level. Moreover, we investigated the effect of 50 μmol/L Indo, a specific inhibitor of COX-2, on H7402-X cells and human immortalized liver L-O2-X cells stably transfected with HBx gene to observe whether HBx enhances proliferation of hepatoma or liver cells via COX-2. BrdU incorporation assay and flow eytometry analysis showed that Indo was able to promote the proliferation of H7402-X cells and L-O2-X cells. Thus, our data demonstrated that HBx enhances the proliferation of hepatoma cells and liver cells through arachidonic acid metabolism mediated by COX-2.

关 键 词：乙型肝炎病毒X蛋白 COX-2 肝癌 肝细胞 细胞增殖 

分 类 号：R364.7[医药卫生—病理学]