title: Candesartan attenuates angiogenesis in hepatocellular carcinoma via downregulating AT1R/VEGF pathway.
abstract: Angiotensin II type 1 receptor (AT1R) was reported to express in many types of tumors, promoting tumor growth and angiogenesis. We herein examined AT1R expression in liver cancer and the potential antitumor effects of AT1R antagonist Candesartan in liver cancer. We found that AT1R expression was positively correlated with VEGF-A expression and microvascular density (MVD) in 40 HCC patients. Angiotensin II and Candesartan neither had effects on the proliferation of liver cancer cells in vitro. However, Angiotensin II upregulated AT1R protein expression and promoted production of VEGF-A in liver cancer cells in a dose-dependent manner. Candesartan was able to reverse this process in a dose-dependent manner. Moreover, Candesartan downregulated the expression of VEGF-A in SMMC-7721 bearing xenografts in mice and inhibited tumor growth and angiogenesis in vivo. Our data suggested that AT1R antagonist Candesartan might be useful to suppress liver cancer by inhibiting angiogenesis.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; Department of Pharmacy, Hanlin College, Nanjing University of Chinese Medicine, Taizhou 225300, China.
authors.forename: Fangtian
authors.initials: F
authors.lastname: Fan
authors.affiliation: Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Tian
authors.affiliation: Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Li
authors.initials: L
authors.lastname: Tao
authors.affiliation: Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Zhaoguo
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Cunsi
authors.initials: C
authors.lastname: Shen
authors.affiliation: Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; Suzhou Traditional Chinese Medical Research Institute, The Affiliated Suzhou Hospital of TCM of Nanjing University of TCM, Suzhou 215003, China. Electronic address: guorongjiang@hotmail.com.
authors.forename: Guorong
authors.initials: G
authors.lastname: Jiang
authors.affiliation: Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: profyinlu@163.com.
authors.forename: Yin
authors.initials: Y
authors.lastname: Lu
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000473:pathology; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D042461:Vascular Endothelial Growth Factor A; D000804:Angiotensin II; C081643:candesartan
keywords: AT(1)R antagonist; Angiotensin II; Candesartan; Hepatocytes; Liver cancer; Tumor angiogenesis