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AAV-Mediated angiotensin 1-7 overexpression inhibits tumor growth of lung cancer in vitro and in vivo

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机构: [1]School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, Guangdong, China. [2]Department of Urology, The First Affiliated Hospital of Clinical Medicine of Guangdong Pharmaceutical University, Guangzhou, Guangdong, China. [3]Department of Clinical Pathology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China. [4]Deparement of Nuclear Medicine, People's Hospital of Yuxi City, Yuxi, Yunnan, China. [5]Department of Biomedical Engineering, The Johns University School of Medicine, Baltimore, USA. [6]Departments of Physiology and Functional Genomics, University of Florida, Gainesville, Florida, USA.
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关键词: Ang-(1-7) lung cancer adeno-associated viral vector DNA synthesis proliferation

摘要:
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.

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大类 | 2 区 医学
小类 | 2 区 肿瘤学 3 区 细胞生物学
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第一作者机构: [1]School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, Guangdong, China.
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