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

• DOI: 10.1038/gt.2017.2
• Publication Date: 2017-01-11T15:41:17Z
• Authors: W Zhou; S Dai; H Zhu; Z Song; Y Cai; J B Lee; Z Li; X Hu; B Fang; C He; X Huang
• Keywords: Gene Expression Regulation, Viral; Oncolytic Virotherapy; Genetic Vectors; Apoptosis; Xenograft Model Antitumor Assays; Adenoviridae; 3. Good health; TNF-Related Apoptosis-Inducing Ligand; Mice; Oncolytic Viruses; 03 medical and health sciences; 0302 clinical medicine; Stomach Neoplasms; Cell Line, Tumor; Animals; Humans; Adenovirus E1A Proteins; Telomerase; Peritoneal Neoplasms; Cell Proliferation

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.