title: AAV-Mediated angiotensin 1-7 overexpression inhibits tumor growth of lung cancer in vitro and in vivo.
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.
authors.affiliation: School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Xinglu
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Urology, The First Affiliated Hospital of Clinical Medicine of Guangdong Pharmaceutical University, Guangzhou, Guangdong, China.
authors.forename: Sansan
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Clinical Pathology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China.
authors.forename: Nana
authors.initials: N
authors.lastname: Pei
authors.affiliation: School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Mao
authors.affiliation: School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Shengyao
authors.initials: S
authors.lastname: Wang
authors.affiliation: School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Renhe
authors.initials: R
authors.lastname: Yan
authors.affiliation: Deparement of Nuclear Medicine, People's Hospital of Yuxi City, Yuxi, Yunnan, China.
authors.forename: Na
authors.initials: N
authors.lastname: Bai
authors.affiliation: Department of Biomedical Engineering, The Johns University School of Medicine, Baltimore, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Li
authors.affiliation: School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Du
authors.affiliation: School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Baihong
authors.initials: B
authors.lastname: Chen
authors.affiliation: Departments of Physiology and Functional Genomics, University of Florida, Gainesville, Florida, USA.
authors.forename: Colin
authors.initials: C
authors.lastname: Sumners
authors.affiliation: School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Jinlong
authors.initials: J
authors.lastname: Li
authors.affiliation: School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Li
mesh_terms: D000803:Angiotensin I / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000473:pathology*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D004261:DNA Replication; D000229:Dependovirus / Q000235:genetics*; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000098:blood supply / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009097:Multienzyme Complexes / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology; D009687:Nuclear Proteins / Q000378:metabolism*; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D059748:Proteolysis; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: C103706:CDC6 protein, human; D018797:Cell Cycle Proteins; D009097:Multienzyme Complexes; D009687:Nuclear Proteins; D010446:Peptide Fragments; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000803:Angiotensin I; C118790:angiotensin I (1-7)
keywords: Ang-(1-7); DNA synthesis; adeno-associated viral vector; lung cancer; proliferation