Ad-mda-7联合多柔比星对人肝癌裸鼠移植瘤的协同抑制作用  

Synergistic inhibitory effects of adenovirus-mediated mda-7 and/or adriamycin on xenografted human hepatocellular carcinoma in nude mice

作　　者：陈堃[1] 薛新波[1] 王从俊[2] 郑建伟[1] 于愿[1] 吉文伟[1] 彭志海[2] 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中心,武汉430030 [2]上海交通大学附属第一人民医院外科,上海200080

出　　处：《肿瘤》2008年第8期681-684,共4页Tumor

基　　金：湖北省科技攻关资助项目(编号:2006AA30/B52-4)

摘　　要：目的:将重组腺病毒介导的黑素瘤分化相关基因-7(melanoma differentiation-associated gene-7,mda-7)/IL-24与多柔比星(adriamycin,ADM)联合治疗人肝癌细胞裸鼠移植瘤,探索基因治疗和化疗相结合治疗肝癌的新方法。方法:构建携带人mda-7/IL-24基因的重组腺病毒载体(Ad-mda-7),单独使用该载体或ADM以及两者联合使用对人肝癌细胞裸鼠移植瘤进行治疗,观察抗肿瘤效果。用免疫组织化学方法检测各组肿瘤组织中基质金属蛋白酶-2(matrix metalloproteinase,MMP-2)与转化生长因子(transforming growth factor,TGF)-β1的表达。结果:成功构建重组腺病毒并实现体内表达,Ad-mda-7+ADM联合治疗组的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<0.01);Ad-mda-7+ADM组裸鼠移植瘤平均大小与单独使用ADM或Ad-mda-7相比明显缩小(P<0.01)。Ad-mda-7能显著降低TGF-β1和MMP-2的表达,明显优于ADM组(P<0.01)。结论:重组腺病毒介导mda-7/IL-24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 investigate the effects of adenovirus-mediated melanoma differentiation-associated gene （mda-7/IL- 24） combined with adriamycin on human hepatocellular carcinoma xenograft in nude mice and to explore a novel method （ gene therapy plus chemotherapy） for hepatoma treatment. Methods： The recombinant adenovirus vector carrying mda-7/IL-24 gene （Ad-mda-7） was constructed. The tumor-bearing nude mice were treated with Ad-mda-7, ADM, or Ad-mda-7 plus ADM, respectively. The anti-tumor effects were observed. The expression of matrix metalloproteinase-2 （ MMP-2 ） and transforming growth factor （TGF） β1 in tumor tissues was detected by immunohistochemistry. Results： Ad-mda-7 was successfully constructed and expressed in vivo. The average survival time of nude mice treated with Ad-mda-7 plus adriamycin was （83.8 ± 4.82） d, which was significantly elongated compared with the other three groups （P 〈0.01 ）. The average volume of xenografted tumor treated with Ad-mda-7 plus adriamycin was significantly reduced compared with that treated with ADM or Ad-mda-7 alone （P 〈 0.01 ）. Ad-mda-7 markedly decreased the expressions of TGF-131 and MMP-2 protein than adriamycin （P 〈 0.01 ）. Conclusion： Ad-mda-7 combined with adriamycin has strong antiumor potency and synergistic effects on human hepatocellular carcinoma xenograft in nude mice. The mechanism is probably related with anti-invasion and anti-metastasis actions.

关 键 词：癌 肝细胞 基因 肿瘤抑制 抗肿瘤联合化疗方案 动物实验 

分 类 号：R735.7[医药卫生—肿瘤]