腺病毒介导MDA-7联合多柔比星对裸鼠移植肝癌作用机制的探讨  

Expressions of VEGF and E-cadherin in hepatocellular carcinoma of nude mice treated by adenovirus-mediated MDA-7 and doxorubicin

作　　者：薛新波[1] 陈堃[1] 王从俊[1] 李雁[2] 郑建伟[1] 吉文伟[1] 于愿[1] 吴在德[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院胆胰外科,湖北武汉430030 [2]武汉大学中南医院肿瘤科武汉大学肿瘤防治研究中心,湖北武汉430000

出　　处：《中华肿瘤防治杂志》2008年第21期1617-1620,共4页Chinese Journal of Cancer Prevention and Treatment

基　　金：湖北省科技攻关资助项目(2006AA304B04-2)

摘　　要：目的:将重组腺病毒介导的MDA-7(melanoma differentiation-associ8ated gene-7)与多柔比星联合治疗裸鼠肝癌,探讨基因治疗和化疗相结合治疗肿瘤的新方法。方法:构建携带人MDA-7的重组腺病毒载体(Ad.MDA-7),单独使用该载体或多柔比星以及两者联合使用对实验性肝癌裸鼠进行治疗,观察抗肿瘤效果。用免疫组化方法检测各组肿瘤组织中VEGF与E钙粘素(E-cadherin)的表达情况。结果:成功构建重组腺病毒并实现体内表达,Ad.MDA-7+多柔比星联合治疗组裸鼠平均生存时间为(83.8±4.82)d,与其他3组相比生存期明显延长,P=0.000 1;Ad.MDA-7+多柔比星组裸鼠肝癌平均大小与单独使用多柔比星或Ad.MDA-7相比明显缩小,P=0.003 1。E-cadherin的表达表明,MDA-7的作用弱于多柔比星;VEGF的表达则显示,MDA-7作用明显优于多柔比星,P=0.016 5。结论:重组腺病毒介导MDA-7联合多柔比星对裸鼠人肝癌转移模型有明显的抗肿瘤作用及协同效应,其机制可能与抗肿瘤侵袭转移有关。OBJECTIVE： To study the effects of adenovirus-mediated MDA-7 and doxorubicin on hepatoma in nude mice and explore a new way for hepatoma gene therapy combined with chemotherapy. METHODS： The recombinant adenovirus vector carrying melanoma differentiation-associated gene-7 （ Ad. MDA-7） was constructed. Ad. MDA 7 and Doxorubicin were in jected into the tumor-bearing mice. The effects on the growth of the tumor and the survival rate of the mice were observed. The expression of VEGF/E-cadherin was detected by an immunohistochemistric method. RESULTS： Ad. MDA-7 was constructed and expressed in vivo. Compared with the other three groups, the mice treated with Ad. MDA-7 combined with doxorubicin had long average survival time （83.8±4.82）d （P=0. 000 1）. The average size of tumor treated with Ad. MDA-7 combined with doxorubicin diminished significantly compared with that treated with doxorubicin or Ad. MDA 7 separately （P= 0. 003 1）. The expression of E cadherin protein increased more in doxorubicin group than in the Ad. MDA7 group, but oppositely in the expression of VEGF （P= 0. 016 5）. CONCLUSIONS： Ad. MDA7 combined with doxorubicin has a strong antitumor potency and synergistic effect on metastastie hepatoma mouse model, and the mechanism of the effect probably relates to anti-metastasis.

关 键 词：肝肿瘤 实验性 基因 MDA 多柔比星 癌 肝细胞 疾病模型 动物 基因疗法 

分 类 号：R735.7[医药卫生—肿瘤]