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

Adenovirus vector-mediated expression of TMEM166 inhibits human cancer cell growth by autophagy and apoptosis in vitro and in vivo
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DOI:
10.1016/j.canlet.2012.08.032
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发表时间:
2013-01-01
期刊:
影响因子:
9.7
通讯作者:
Chen, Yingyu
Chen, Yingyu
中科院分区:
医学1区
文献类型:
--
作者:
Chang, Ying;Li, Yanjun;Chen, Yingyu

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TMEM 166是一种新的程序性细胞死亡相关分子。本研究构建了5-TMEM 166重组腺病毒载体(Ad 5-TMEM 166),并对其进行了体内外表达和抗肿瘤活性的研究。细胞活力分析显示,腺病毒介导的TMEM 166的增加以剂量和时间依赖性方式抑制肿瘤细胞生长。这种抑制作用由自噬(通过mTOR的抑制和p70 S6 K的激活)和凋亡(通过半胱天冬酶-3的激活)介导,这两者都有助于细胞死亡和致瘤性的抑制。我们的数据表明,Ad 5-TMEM 166可能是一种新的肿瘤基因治疗候选。(C)2012爱思唯尔爱尔兰有限公司保留所有权利。
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.