Zhou W, Dai S, Zhu H, Song Z, Cai Y, Lee J B, Li Z, Hu X, Fang B, He C, Huang X
Department of Colorectal Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Key Laboratory of Biotherapy of Zhejiang province, Hangzhou, China.
Gene Ther. 2017 Apr;24(4):199-207. doi: 10.1038/gt.2017.2. Epub 2017 Jan 11.
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.
腹膜播散是胃癌最常见的转移情况。晚期胃癌患者的生存时长可通过基因治疗得到改善。在本研究中,我们使用了一种溶瘤腺病毒载体(Ad/TRAIL-E1),其在肿瘤特异性启动子的控制下表达TRAIL和E1A基因。我们评估了Ad/TRAIL-E1在体外对胃癌细胞的抗肿瘤作用,以及在异种移植腹膜癌病小鼠模型中的体内抗肿瘤作用。我们的数据表明,Ad/TRAIL-E1在胃癌细胞系中诱导了TRAIL介导的凋亡,但在正常细胞系中未诱导。此外,Ad/TRAIL-E1显著抑制了腹膜转移并延长了小鼠的生存期,且无治疗相关毒性。因此,来自溶瘤腺病毒载体的肿瘤特异性TRAIL表达可能为治疗伴有腹膜播散的晚期胃癌提供一种新的治疗方法。