title: Overexpression of ACE2 produces antitumor effects via inhibition of angiogenesis and tumor cell invasion in vivo and in vitro.
abstract: Angiotensin II (AngII) is a multifunctional bioactive peptide in the renin-angiotensin system (RAS). Angiotensin-converting enzyme 2 (ACE2) is a newly identified component of RAS. The role of AngII and ACE2 in the metastasis of non-small cell lung cancer (NSCLC) and the effects on matrix metalloproteinases (MMPs) are still unknown. In the present study, the anti-invasive effect and mechanism of ACE2 were investigated in vitro and in vivo. Results of a transwell assay showed that the overexpression of ACE2 reduces the invasive ability of A549 cells in vitro. According to the results of qRT-PCR and western blot analysis, the inhibitory role of ACE2 was mediated through the down-regulation of MMP-2 and MMP-9. Additionally, we confirmed that the overexpression of ACE2 inhibited cell growth and VEGFa production while simultaneously suppressing ACE and angiotensin II type 1 receptor (AT1R) expression in human lung cancer xenografts. These results suggest that the overexpression of ACE2 may potentially suppress the invasion and angiogenesis of NSCLC.
authors.affiliation: Department of Respiration, Shanghai Institute of Endocrinology, State Key Laboratory of Medical Genomics, Shanghai 200025, PR China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Feng
authors.forename: Lei
authors.initials: L
authors.lastname: Ni
authors.forename: Huanying
authors.initials: H
authors.lastname: Wan
authors.forename: Liang
authors.initials: L
authors.lastname: Fan
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Fei
authors.forename: Qinyun
authors.initials: Q
authors.lastname: Ma
authors.forename: Beili
authors.initials: B
authors.lastname: Gao
authors.forename: Yi
authors.initials: Y
authors.lastname: Xiang
authors.forename: Jiaming
authors.initials: J
authors.lastname: Che
authors.forename: Qingyun
authors.initials: Q
authors.lastname: Li
mesh_terms: D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007703:Peptidyl-Dipeptidase A / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction; D014161:Transduction, Genetic; D023041:Xenograft Model Antitumor Assays
chemical_list: D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; C000705328:Ace2 protein, mouse; D000085962:Angiotensin-Converting Enzyme 2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9