Synergistic gastric cancer inhibition by chemogenetherapy with recombinant human adenovirus p53 and epirubicin: an in vitro and in vivo study |
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Authors: | Xie Yi-Shan Zhang Yan-Hua Liu Shao-Ping Liu Shi-Quan Peng Chun-Wei Wu Long Luo He-Shen Li Yan |
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Institution: | Department of Oncology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China. |
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Abstract: | This study was designed to investigate the in vitro and in vivo antitumor effect on SGC-7901 gastric cancer cells by chemogenetherapy. SGC-7901 cells were treated by chemogenetherapy with Gendicine, a recombinant human Ad-p53 injection (rAd-p53), and epirubicin hydrochloride (EPI), a cytotoxic chemotherapy agent. Compared with blank control, rAd-p53, EPI, and combined therapy achieved SGC-7901 growth inhibition by 32.26, 35.48, 43.44%, respectively on day 1 and 70.62, 78.82, 87.15%, respectively on day 2 (rAd-p53, EPI VS control, p<0.01; rAd-p53+EPI VS either alone, p<0.05). Flow cytometry study confirmed that rAd-p53 and/or EPI mainly inhibit the cell cycle at S phase. SGC-7901 cells were subcutaneously injected into the nude mice to form xenograft models, which were treated with rAd-p53 and EPI. Compared with the blank control, treatment with rAd-p53 at the dose of 10 μl of 10(12) vp/ml and EPI at the dose of 1.25 mg/kg, 7 times in 3 weeks, resulted in 80 and 60% of tumor growth inhibition, respectively. No animal death was observed, although 2 nude mice in rAd-p53 group developed liver toxicity and 1 nude mouse in EPI group developed cardiac toxicity. rAd-p53 and EPI have synergistic tumor inhibition effect on gastric cancer cells. |
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