Combined use of adenoviral vector Ad5/F35-mediated APE1 siRNA enhances the therapeutic efficacy of adenoviral-mediated p53 gene transfer in hepatoma cells in vitro and in vivo

Cun,Yanping; Zhang,Qinhong; Xiong,Chengjie; Li,Mengxia; Dai,Nan; Zhang,Shiheng; Wang,Dong

doi:10.3892/or.2013.2384

Combined use of adenoviral vector Ad5/F35-mediated APE1 siRNA enhances the therapeutic efficacy of adenoviral-mediated p53 gene transfer in hepatoma cells in vitro and in vivo

Authors:
- Yanping Cun
- Qinhong Zhang
- Chengjie Xiong
- Mengxia Li
- Nan Dai
- Shiheng Zhang
- Dong Wang
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Affiliations: Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, P.R. China, Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, P.R. China
Published online on: April 4, 2013 https://doi.org/10.3892/or.2013.2384
Pages: 2197-2204

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Abstract

Gene therapy has emerged as a novel therapeutic approach for the treatment of cancer. In order to establish a more effective therapeutic strategy against unresectable hepatocellular carcinoma (HCC), we evaluated, in the present study, the effects of combined treatment with adenoviral vector Ad5/F35-mediated APE1 siRNA (Ad5/F35-siAPE1) and adenoviral-mediated p53 gene transfer (Ad-p53) in hepatoma cells in vitro and in vivo. Infection of SMMC-7721 cells with Ad5/F35-siAPE1 resulted in a time- and dose-dependent decrease of APE1 protein, while Ad-p53 treatment led to a time- and dose-dependent increase of p53 protein expression. Ad5/F35-siAPE1 significantly enhanced the cytotoxic effect of SMMC-7721 cells to Ad-p53 in cell survival assays, associated with increased cell apoptosis. Moreover, administration of Ad5/F35-siAPE1 and Ad-p53 into nude mice resulted in tumor growth inhibition and apoptosis induction in SMMC-7721 xenografts compared to administration of either agent alone. These results suggest that combination of Ad5/F35-siAPE1 and Ad-p53 could be a promising gene therapeutic approach against human HCC.

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