Oncolytic adenovirus-mediated E1A gene therapy induces tumor-cell apoptosis and reduces tumor angiogenesis leading to inhibition of hepatocellular carcinoma growth in animal model.
Oncolytic adenovirus (rAd)-mediated E1A gene therapy of cancer has become a novel therapeutic modality. In this study, we constructed a recombinant oncolytic adenovirus (rAd-E1A) expressing the tumor suppressor E1A gene. We demonstrated that the rAd-E1A replicated in HepG2 and SMMC-7721 human hepatocellular carcinoma (HCC) cells but attenuated in the normal liver cell line HL-7702. It induced HCC cell apoptosis through upregulation of apoptosis-associated Bax, caspase-3, and Fas and downregulation of survivin and Bcl-2 in a p53-dependent pathway. It also downregulated the expression of angiogenesis- associated vascular endothelial growth factor (VEGF) and CD34 genes and reduced tumor vessel formation and angiogenesis. In mice bearing SMMC-7721 tumors, intratumoral injections of rAd- E1A significantly inhibited HCC growth. Therefore, the oncolytic adenovirus-mediated E1A gene therapy may be a useful therapeutic approach for HCC treatment.
Ye
Zhenmin
Z
Cell and Molecular Biology Institute, College of Medicine, Soochow University, SuZhou, China.
Wang
Xiaohua
X
Hao
Siguo
S
Zhong
Jiang
J
Xiang
Jim
J
Yang
Jicheng
J
D017500:Adenovirus E1A Proteins / Q000235:genetics*; D000818:Animals; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000628:therapy*; D002460:Cell Line; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D009389:Neovascularization, Pathologic; D050504:Oncolytic Viruses / Q000235:genetics*
D017500:Adenovirus E1A Proteins