Adenovirus vector-mediated expression of TMEM166 inhibits human cancer cell growth by autophagy and apoptosis in vitro and in vivo

被引:42
作者
Chang, Ying [1 ,2 ]
Li, Yanjun [1 ,2 ]
Hu, Jia [1 ,2 ]
Guo, Jinhai [3 ]
Xu, Dong [1 ,2 ]
Xie, Hong [1 ]
Lv, Xiaodong [1 ]
Shi, Taiping [3 ]
Chen, Yingyu [1 ,2 ]
机构
[1] Peking Univ, Hlth Sci Ctr, Minist Hlth, Key Lab Med Immunol, Beijing 100191, Peoples R China
[2] Peking Univ, Ctr Human Dis Genom, Beijing 100191, Peoples R China
[3] Chinese Natl Human Genome Ctr, Beijing, Peoples R China
基金
中国国家自然科学基金;
关键词
TMEM166; Adenovirus vector; Autophagy; Apoptosis; Anti-tumor activity; TUMOR-SUPPRESSOR; PROTEIN; BECLIN-1; DEATH; GENE; MACROAUTOPHAGY; TUMORIGENESIS; THERAPY; COMPLEX; KINASE;
D O I
10.1016/j.canlet.2012.08.032
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
TMEM166 is a novel programmed cell death-related molecule. In this report, we constructed a recombinant adenovirus 5-TMEM166 vector (Ad5-TMEM166) and evaluated its expression and anti-tumor activities in vitro and in vivo. Cell viability analysis revealed that the adenovirus-mediated increase of TMEM166 inhibited tumor cell growth in a dose- and time-dependent manner. This inhibitory effect was mediated by both autophagy (via inhibition of mTOR and activation of p70S6K) and apoptosis (via caspase-3 activation), both of which contributed to cell death and suppression of tumorigenicity. Our data indicated that Ad5-TMEM166 may be a novel gene therapy candidate for cancer. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:126 / 134
页数:9
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