Original Article | Published:

Telomerase-specific oncolytic adenovirus expressing TRAIL suppresses peritoneal dissemination of gastric cancer

Gene Therapy volume 24, pages 199207 (2017) | Download Citation

Abstract

Peritoneal dissemination is the most common condition of metastasis in gastric cancer. The survival duration of a patient with advanced stage gastric cancer, may be improved by gene therapy. In this study, we used an oncolytic adenovirus vector (Ad/TRAIL-E1) that expresses both the TRAIL and E1A genes under the control of a tumor-specific promoter. We evaluated the anti-tumor effect of Ad/TRAIL-E1 on gastric cancer cells in vitro, as well as in vivo in a xenograft peritoneal carcinomatosis mouse model. Our data showed that Ad/TRAIL-E1 induced TRAIL-mediated apoptosis in gastric cancer cell lines, but not in the normal cell lines. In addition, Ad/TRAIL-E1 significantly inhibited peritoneal metastasis and prolonged the survival of mice without treatment-related toxicity. Therefore, tumor-specific TRAIL expression from an oncolytic adenovirus vector may provide a novel therapeutic approach for the treatment of advance stage gastric cancer with peritoneal dissemination.

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Acknowledgements

We thank Dr Yongqiang Liao for his assistance in pathology evaluation. This work was supported by the National Natural Science Foundation of China grant 81402580, 81370461 and 81272681.

Author information

Author notes

    • W Zhou
    •  & S Dai

    These authors contributed equally to this work.

Affiliations

  1. Department of Colorectal Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China

    • W Zhou
    • , S Dai
    • , H Zhu
    • , Z Song
    • , C He
    •  & X Huang
  2. Key Laboratory of Biotherapy of Zhejiang province, Hangzhou, China

    • W Zhou
    • , S Dai
    • , H Zhu
    • , Z Song
    • , X Hu
    •  & C He
  3. Department of Biochemistry and Molecular Medicine, The George Washington University Medical School, Washington, DC, USA

    • Y Cai
    • , J B Lee
    •  & Z Li
  4. Department of Thoracic and Cardiovascular Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA

    • B Fang

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Competing interests

The authors declare no conflicts of interest.

Corresponding author

Correspondence to X Huang.

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DOI

https://doi.org/10.1038/gt.2017.2

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