带有CMV、CEA启动子的腺病毒载体介导TK基因在肿瘤细胞中的表达特性  

Characteristics of Adenovirus Vector Mediated TK-gene Expression Promoted by CMV and CEA Promoters in Tumor Cells

作　　者：冯宇新[1] 房欣[1] 史国利[1] 董元舒[1] 王文俊[1] 陈德风[1] 

机构地区：[1]南开大学分子生物学研究所,天津300071

出　　处：《基础医学与临床》1999年第5期32-36,共5页Basic and Clinical Medicine

基　　金：国家自然科学资金!39670410

摘　　要：TK基因一GCV系统是最有希望在临床上用于肿瘤基因治疗的方法之一。为了提高基因靶向表达的效率，使之可以应用于体内实验，我们构建重组腺病毒AdCMVTK和带有CMV、CEA两个启动子的AdCMVCEATK，在五种癌细胞中进行了体外实验。发现腺病毒介导的TK基因赋予癌细胞GCV敏感性比对照组高2～3个数量级，并使感染病毒和未感染病毒细胞比例为110时仍产生较强的“旁观效应”。实验表明PG肺癌，CAn结肠癌，HeLa细胞是腺病毒介导的TK基因的理想靶细胞。Transfer of herpes simplex virus thyrnidine gene (HSVTK) into tumor cells provides a potentialstrategy for the treatment of malignancy. Because of the limitation of using retrovirus vectors forclinical application, the feasibilty of using a recombinan adenovirus containing HSVTK was examined.A recombinant adenovirus (AdCMVTK) and a recombinam adenovirus that contains both CMV andCEA promoter were constructed to improve th efficiency ofeqeted gene expression and explore thepossibility of applying in vivo. Cell lines derived from five human malignancies (carcinoma) infectedwith AdCMVTK and AdCMVCEATK showed strong sensitivity to ganciclovir that were 2~3 logslower than uninfected cells or those infected with a colltrol virus. A strong ubystander effect wasnoted in tumor cell lines; these was no diminution in the efficacy of GCV treatment until the ratio ofinfected and uninfected cells fell below 1: 10. This study thus demonstrates in vitro efficacy of anadenovirus-transduced HSVTK drug sensitization gene therapy system in PG (lung cancer), CAE(colon carcinoma) and HeLa cells.

关 键 词：肿瘤 基因治疗 P53基因 腺病毒载体 CEA CMV 

分 类 号：R730.5[医药卫生—肿瘤]