Synergistic suppression effect on tumor growth of hepatocellular carcinoma by combining oncolytic adenovirus carrying XAF1 with cisplatin

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• 作者：Buyun Ma (1)
  Yanchun Wang (1)
  Xiumei Zhou (1)
  Panpan Huang (1)
  Rong Zhang (1)
  Tao Liu (1)
  Caixia Cui (2)
  Xinyuan Liu (1)
  Yigang Wang (1)
  
  1. Xinyuan Institute of Medicine and Biotechnology ; College of Life Sciences ; Zhejiang Sci-Tech University ; Hangzhou ; 310018 ; China
  2. Otorhinolaryngology Head and Neck Surgery ; The Affiliated Hospital of Hangzhou Normal University ; Hangzhou ; 310015 ; China
  
• 关键词：Oncolytic adenovirus ; Cisplatin ; XAF1 ; Hepatocellular carcinoma
• 刊名：Journal of Cancer Research and Clinical Oncology
• 出版年：2015
• 出版时间：March 2015
• 年：2015
• 卷：141
• 期：3
• 页码：419-429
• 全文大小：2,020 KB
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• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Oncology
  Cancer Research
  Internal Medicine
  Hematology
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-1335

文摘

Purpose The potent anticancer efficacy of oncolytic viruses has been verified in Clinic in recent years. Cisplatin (DDP) is one of most common chemotherapeutic drugs, but is accompanied by side effects and drug resistance. Our previous studies have shown the strategy of cancer -targeting gene-viro-therapy (CTGVT) mediated by the oncolytic virus ZD55 containing the XAF1 cDNA (ZD55-XAF1), which exhibited potent antitumor effects in various tumor cells and no apparent toxicities on normal cells. In the study, the CTGVT strategy is broadened by combining DDP with ZD55-XAF1 for growth inhibition of hepatocellular carcinoma (HCC) cells. Methods The transgenic expression was evaluated by both in vitro and in vivo experiments, and the enhanced inhibitory effect of ZD55-XAF1 combined with cisplatin was assessed in HCC cells. The cytotoxicity on normal liver cells was evaluated by MTT assay and apoptotic cell staining. Activation of caspase-9 and PARP for apoptosis was further detected by Western blot analysis. The in vivo antitumor efficacy of combination treatment with cisplatin and ZD55-XAF1 was estimated in an HCC xenograft mouse model. Results We found that the combination of ZD55-XAF1 and cisplatin showed enhanced inhibitory effects on the proliferation of HCC cells in vitro and tumor growth in mice. Furthermore, the combined treatment of ZD55-XAF1 and DDP decreases the chemotherapy dose needed to achieve the same inhibitory effect without overlapping toxicities on normal liver cells and induces tumor cell apoptosis via the activation of caspase-9/PARP pathway. Conclusion Thus, these data suggest that the chemo-gene-viro-therapeutic strategy by combining ZD55-XAF1 and DDP reveals a novel therapeutic strategy for hepatocellular carcinoma.