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

被引：27
|
作者：
Zhou, W. [1 ,2 ]
Dai, S. [1 ,2 ]
Zhu, H. [1 ,2 ]
Song, Z. [1 ,2 ]
Cai, Y. [3 ]
Lee, J. B. [3 ]
Li, Z. [3 ]
Hu, X. [2 ]
Fang, B. [4 ]
He, C. [1 ,2 ]
Huang, X. [1 ]
机构：
[1] Zhejiang Univ, Sir Run Run Shaw Hosp, Sch Med, Dept Colorectal Surg, 3 Qingchun East Rd, Hangzhou 310016, Zhejiang, Peoples R China
[2] Key Lab Biotherapy Zhejiang Prov, Hangzhou, Zhejiang, Peoples R China
[3] George Washington Univ, Med Sch, Dept Biochem & Mol Med, Washington, DC USA
[4] Univ Texas MD Anderson Canc Ctr, Dept Thorac & Cardiovasc Surg, Houston, TX 77030 USA
来源：
GENE THERAPY | 2017年 / 24卷 / 04期
基金：
中国国家自然科学基金;
关键词：
GENE-THERAPY; INTRAPERITONEAL CHEMOTHERAPY; CYTOREDUCTIVE SURGERY; TUMOR-GROWTH; CELLS; REPLICATION; PROMOTER; STRATEGIES; APOPTOSIS; LIGAND;
D O I：
10.1038/gt.2017.2
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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/TRAILE1) 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.
引用
收藏
页码：199 / 207
页数：9
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