title: Selective effects of a fiber chimeric conditionally replicative adenovirus armed with hep27 gene on renal cancer cell.
abstract: ASBTARCT Adenoviruses mediated cancer gene therapies are widely investigated and show a promising effect on cancer treatment. However, efficient gene transfer varies among different cancer cell lines based on the expression of coxsakie adenovirus receptor (CAR). Hep27, a member of dehydrogenase/reductase (SDR) family, can bind to Mdm2, resulting in the attenuation of Mdm2-mediated p53 degradation. Here we constructed a fiber chimeric adenovirus carrying hep27 gene (F5/35-ZD55-Hep27), in which the fiber protein of 5-serotype adenovirus (Ad5) was substituted by that of 35-serotype adenovirus (Ad35), aiming to facilitate the infection for renal cancer cells and develop the role of hep27 in cancer therapy. We evaluated the CAR and CD46 (a membrane cofactor protein for Ad35) expression in four kinds of renal cancer cells and assessed the relationship between receptors and infection efficiency. 5/35 fiber-modified adenovirus had a much promising infectivity compared with Ad5-based vector in renal cancer cells. F5/35-ZD55-Hep27 had enhanced antitumor activity against human renal cancer cells compared to the other groups. Further, hep27 mediated p53 and cleaved-PARP upregulation and mdm2 downregulation was involved and caused increased apoptosis. Moreover, F5/35-ZD55-Hep27 significantly suppressed tumor growth in subcutaneous renal cancer cell xenograft models. Our data demonstrated that 5/35 fiber-modified adenovirus F5/35-ZD55-Hep27 transferred into renal cancers efficiently and increased p53 to induce cancer cell apoptosis. Thus 5/35 fiber-modified adenoviral vector F5/35-ZD55-Hep27 might a promising vector and antitumor reagent for renal cancer gene therapy.
authors.affiliation: a Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College , Xuzhou , China.
authors.forename: Lin
authors.initials: L
authors.lastname: Fang
authors.affiliation: a Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College , Xuzhou , China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Cheng
authors.affiliation: a Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College , Xuzhou , China.
authors.forename: Wenshun
authors.initials: W
authors.lastname: Liu
authors.affiliation: a Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College , Xuzhou , China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: a Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College , Xuzhou , China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ge
authors.affiliation: a Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College , Xuzhou , China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: a Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College , Xuzhou , China.|b Cancer Center, Affiliated Hospital of Xuzhou Medical College , Xuzhou , China.
authors.forename: Liantao
authors.initials: L
authors.lastname: Li
authors.affiliation: a Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College , Xuzhou , China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Liu
authors.affiliation: a Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College , Xuzhou , China.|b Cancer Center, Affiliated Hospital of Xuzhou Medical College , Xuzhou , China.|c Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical College , Xuzhou , China.
authors.forename: Junnian
authors.initials: J
authors.lastname: Zheng
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000429:Alcohol Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000074409:Carbonyl Reductase (NADPH); D002292:Carcinoma, Renal Cell / Q000235:genetics*; D046528:Chimerism; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D050130:Oncolytic Virotherapy / Q000379:methods*; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: D009687:Nuclear Proteins; D000429:Alcohol Oxidoreductases; D000074409:Carbonyl Reductase (NADPH); C095961:DHRS2 protein, human
keywords: CAR; CD46; Hep27; fiber chimeric adenovirus; renal cell carcinoma (RCC)