AAV-Mediated angiotensin 1-7 overexpression inhibits tumor growth of lung cancer in vitro and in vivo.
AAV-Mediated angiotensin 1-7 overexpression inhibits tumor growth of lung cancer in vitro and in vivo.
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AAV介导的血管紧张素1-7过表达抑制肺癌体内外肿瘤生长
DOI：
10.18632/oncotarget.13396
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发表时间：
2017-01-03
期刊：
影响因子：
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通讯作者：
Li H
中科院分区：
文献类型：
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作者：
Chen X;Chen S;Pei N;Mao Y;Wang S;Yan R;Bai N;Li A;Zhang Y;Du H;Chen B;Sumners C;Li J;Li H
Ang-（1-7）抑制肺癌细胞生长的实验研究然而，其作用的分子机制尚不清楚，并且Ang-（1-7）在体内的快速降解限制了其临床应用。在这里，我们已经证明，血管紧张素-（1-7）抑制肺癌细胞的生长，通过中断复制前的复合物组装和抑制上皮间充质转化通过Cdc 6抑制。此外，我们构建了一种突变型腺相关病毒载体AAV 8（Y 733 F），在异种移植瘤模型中产生稳定和高效的Ang-（1-7）表达。结果表明，AAV 8介导的Ang-（1-7）过表达可通过下调Cdc 6和抗血管生成来显著抑制体内肿瘤生长。通过AAV 8方法过表达Ang-（1-7）可能是肺癌治疗的有希望的策略。
Ang-(1-7) inhibits lung cancer cell growth both in vitro and in vivo. However, the molecular mechanism of action is unclear and also the rapid degradation of Ang-(1-7) in vivo limits its clinical application. Here, we have demonstrated that Ang- (1-7) inhibits lung cancer cell growth by interrupting pre-replicative complex assembly and restrains epithelial-mesenchymal transition via Cdc6 inhibition. Furthermore, we constructed a mutant adeno-associated viral vector AAV8 (Y733F) that produced stable and high efficient Ang-(1-7) expression in a xenograft tumor model. The results show that AAV8-mediated Ang-(1-7) over-expression can remarkably suppress tumor growth in vivo by down-regulating Cdc6 and anti-angiogenesis. Ang-(1-7) over-expression via the AAV8 method may be a promising strategy for lung cancer treatment.