Research Papers:
AAV-Mediated angiotensin 1-7 overexpression inhibits tumor growth of lung cancer in vitro and in vivo
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Abstract
Xinglu Chen1,*, Sansan Chen2,*, Nana Pei3,*, Yingying Mao1, Shengyao Wang1, Renhe Yan1, Na Bai4, Andrew Li5, Yanling Zhang1, Hongyan Du1, Baihong Chen1, Colin Sumners6, Jinlong Li1, Hongwei Li1
1School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, Guangdong, China
2Department of Urology, The First Affiliated Hospital of Clinical Medicine of Guangdong Pharmaceutical University, Guangzhou, Guangdong, China
3Department of Clinical Pathology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China
4Deparement of Nuclear Medicine, People’s Hospital of Yuxi City, Yuxi, Yunnan, China
5Department of Biomedical Engineering, The Johns University School of Medicine, Baltimore, USA
6Departments of Physiology and Functional Genomics, University of Florida, Gainesville, Florida, USA
*These authors contributed equally to this work
Correspondence to:
Hongwei Li, email: [email protected]
Jinglong Li, email: [email protected]
Keywords: Ang-(1-7), lung cancer, adeno-associated viral vector, DNA synthesis, proliferation
Received: October 07, 2016 Accepted: November 11, 2016 Published: November 16, 2016
ABSTRACT
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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