title: Angiotensin-(1-7) Decreases Cell Growth and Angiogenesis of Human Nasopharyngeal Carcinoma Xenografts.
abstract: Angiotensin-(1-7) [Ang-(1-7)] is an endogenous, heptapeptide hormone acting through the Mas receptor (MasR), with antiproliferative and antiangiogenic properties. Recent studies have shown that Ang-(1-7) has an antiproliferative action on lung adenocarcinoma cells and prostate cancer cells. In this study, we report that MasR levels were significantly upregulated in nasopharyngeal carcinoma (NPC) specimens and NPC cell lines. Viral vector-mediated expression of Ang-(1-7) dramatically suppressed NPC cell proliferation and migration in vitro. These effects were completely blocked by the specific Ang-(1-7) receptor antagonist A-779, suggesting that they are mediated by the Ang-(1-7) receptor Mas. In this study, Ang-(1-7) not only caused a significant reduction in the growth of human nasopharyngeal xenografts, but also markedly decreased vessel density, suggesting that the heptapeptide inhibits angiogenesis to reduce tumor size. Mechanistic investigations revealed that Ang-(1-7) inhibited the expression of the proangiogenic factors VEGF and PlGF. Taken together, the data suggest that upregulation of MasR could be used as a diagnostic marker of NPC and Ang-(1-7) may be a novel therapeutic agent for nasopharyngeal cancer therapy because it exerts significant antiangiogenic activity.
authors.affiliation: School of Biotechnology, Southern Medical University, Guangzhou, Guangdong, China. 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: Department of Otolaryngology-Head and Neck Surgery, Guangdong NO.2 Provincial People's Hospital, Guangzhou, Guangdong, China.
authors.forename: Renqiang
authors.initials: R
authors.lastname: Wan
authors.affiliation: School of Biotechnology, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Xinglu
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Biomedical Engineering, The Johns University School of Medicine, Baltimore, Maryland.
authors.forename: Andrew
authors.initials: A
authors.lastname: Li
authors.affiliation: School of Biotechnology, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Biotechnology, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Jinlong
authors.initials: J
authors.lastname: Li
authors.affiliation: School of Biotechnology, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Du
authors.affiliation: School of Biotechnology, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Baihong
authors.initials: B
authors.lastname: Chen
authors.affiliation: Beijing Minhai Biotechnology Co. Ltd., Beijing, China.
authors.forename: Wenjin
authors.initials: W
authors.lastname: Wei
authors.affiliation: Department of Physiology and Functional Genomics, University of Florida, Gainesville, Florida.
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Qi
authors.affiliation: Department of Pharmacology, University of Florida, Gainesville, Florida.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pharmacodynamics, University of Florida, Gainesville, Florida.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Katovich
authors.affiliation: Department of Physiology and Functional Genomics, University of Florida, Gainesville, Florida.
authors.forename: Colin
authors.initials: C
authors.lastname: Sumners
authors.affiliation: Beijing Minhai Biotechnology Co. Ltd., Beijing, China. zhenghaifa@sina.com hongwei1@yahoo.com.
authors.forename: Haifa
authors.initials: H
authors.lastname: Zheng
authors.affiliation: School of Biotechnology, Southern Medical University, Guangzhou, Guangdong, China. zhenghaifa@sina.com hongwei1@yahoo.com.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Li
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000803:Angiotensin I / Q000494:pharmacology*; D000818:Animals; D002277:Carcinoma; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D010446:Peptide Fragments / Q000494:pharmacology*; D000090063:Proto-Oncogene Mas; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C000715470:MAS1 protein, human; D008565:Membrane Proteins; C098069:PIGF protein, human; D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D042461:Vascular Endothelial Growth Factor A; D000803:Angiotensin I; D040262:Receptors, Vascular Endothelial Growth Factor; C118790:angiotensin I (1-7)