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

Telomerase-specific oncolytic adenovirus expressing TRAIL suppresses peritoneal dissemination of gastric cancer
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表达TRAIL的端粒酶特异性溶瘤腺病毒抑制胃癌腹膜播散

DOI:
10.1038/gt.2017.2
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发表时间:
2017-01
期刊:
影响因子:
5.1
通讯作者:
Huang X.
Huang X.
中科院分区:
医学3区
文献类型:
--
作者:
Zhou W.;Dai S.;Zhu H.;Song Z.;Cai Y.;Lee J. B.;Li Z.;Hu X.;Fang B.;He C.;Huang X.

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腹膜播散是胃癌最常见的转移方式。基因治疗可提高晚期胃癌患者的生存期。在这项研究中,我们使用了一种溶瘤腺病毒载体(Ad/TRAIL- e1),它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在体外和体内对胃癌细胞的抗肿瘤作用,以及在异种移植腹膜癌小鼠模型中的抗肿瘤作用。我们的数据显示,Ad/TRAIL-E1在胃癌细胞系中诱导trail介导的细胞凋亡,而在正常细胞系中没有。此外,Ad/TRAIL-E1显著抑制腹膜转移,延长小鼠生存期,无治疗相关毒性。因此,从溶瘤腺病毒载体中表达肿瘤特异性TRAIL可能为晚期胃癌腹膜播散治疗提供一种新的治疗方法。
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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