Recombinant adenovirus vector-mediated human MDA-7 gene transfection suppresses hepatocellular carcinoma growth in a mouse xenograft model  

作　　者：Xinting Pan Liqun Wu Jingyu Cao Weidong Guo Zusen Wang Bing Han Weiyu Hu 

机构地区：[1]Department of Hepatohiliary Surgery, the Aft~liated Hospital of Medical College of Qingdao University, Qingdao, Shandong 266000, China.

出　　处：《The Journal of Biomedical Research》2012年第1期53-58,共6页生物医学研究杂志（英文版）

基　　金：supported by grants from Shandong Province Postdoctoral Innovation Project Special Foundation (No.201003048);the Postdoctoral Science Foundation of China (No.2011M500697)

摘　　要：Hepatocellular carcinoma is one of the most common tumors in the world. The purpose of the present study was to investigate the inhibitory effects of adenoviral transduction of human melanoma differentiation-associated gene-7 （MDA-7） gene on hepatocellular carcinoma, so as to provide a theoretical basis for gene therapy of the disease. The human MDA-7 gene was cloned into replication-defective adenovirus specific to HepG2 cells us- ing recombinant virus technology. RT-PCR and Western blotting assays were used to determine the expression of human MDA-7 mRNA and MDA-7 protein in HepG2 cells in vitro. Induction of apoptosis by overexpression of the human MDA-7 gene was determined by flow cytometry. In-vivo efficacy of adenoviral delivery of the hu- man MDA-7 gene was assessed in nude mice beating HepG2 cell lines in vivo by determining inhibition of tumor growth, VEGF and CD34 expression, and microvascular density （MVD）. The results showed that AdGFP/MDA- 7 induced apoptosis of HepG2 cells in vitro and significantly inhibited tumor growth in vivo （P 〈 0.05）. The intra- tumoral MVD decreased significantly in the treated tumors （P 〈 0.05）. We conclude the recombination adenovirus AdGFP/MDA-7 can effectively express biologically active human MDA-7, which leads to inhibition of hepatocel- lular carcinoma growth.Hepatocellular carcinoma is one of the most common tumors in the world. The purpose of the present study was to investigate the inhibitory effects of adenoviral transduction of human melanoma differentiation-associated gene-7 （MDA-7） gene on hepatocellular carcinoma, so as to provide a theoretical basis for gene therapy of the disease. The human MDA-7 gene was cloned into replication-defective adenovirus specific to HepG2 cells us- ing recombinant virus technology. RT-PCR and Western blotting assays were used to determine the expression of human MDA-7 mRNA and MDA-7 protein in HepG2 cells in vitro. Induction of apoptosis by overexpression of the human MDA-7 gene was determined by flow cytometry. In-vivo efficacy of adenoviral delivery of the hu- man MDA-7 gene was assessed in nude mice beating HepG2 cell lines in vivo by determining inhibition of tumor growth, VEGF and CD34 expression, and microvascular density （MVD）. The results showed that AdGFP/MDA- 7 induced apoptosis of HepG2 cells in vitro and significantly inhibited tumor growth in vivo （P 〈 0.05）. The intra- tumoral MVD decreased significantly in the treated tumors （P 〈 0.05）. We conclude the recombination adenovirus AdGFP/MDA-7 can effectively express biologically active human MDA-7, which leads to inhibition of hepatocel- lular carcinoma growth.

关 键 词：MDA-7 ADENOVIRUS hepatocellular carcinoma gene therapy angiogenesis 

分 类 号：Q782[生物学—分子生物学] S858.285.3[农业科学—临床兽医学]