title: Loss of angiotensin-converting enzyme 2 promotes growth of gallbladder cancer.
abstract: The aim of this study is to investigate the role of angiotensin-converting enzyme 2 (ACE2) in gallbladder cancer (GBC) and the therapeutic potential of angiotensin receptor blocker in GBC. Human gallbladder epithelial cells (HGBEC) together with GBC cells and tissue samples were used. In vitro studies were carried out to investigate the role of ACE2 in GBC cells. ACE2 levels were studied in in vivo GBC mouse models subject to ARB treatment. ACE2 level was decreased in GBC cells compared with that in normal gallbladder cells. Replenishment of angiotensin II (A2) promoted tumour cell growth, which could be mitigated by ACE2 supplement. ARB blocked A2-induced GBC cell growth and activated ERK. Activity of mTOR was not altered with different ACE2 status. ARB inhibited tumour growth in xenograft mouse models. In vivo study also showed that decreased expression of ACE2 was associated with enlarged tumour size. By genetic replenishment of ACE2 and pharmaceutical use of ARB, restored ACE2 level mitigated GBC growth. Our results supported the rationale for the use of ARB in GBC patients for potential therapeutic benefit.
authors: Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, 200040, People's Republic of China.
authors: Huajie
authors: H
authors: Zong
authors: Baobing
authors: B
authors: Yin
authors: Huading
authors: H
authors: Zhou
authors: Duan
authors: D
authors: Cai
authors: Baojin
authors: B
authors: Ma
authors: Yang
authors: Y
authors: Xiang
mesh_terms: D057911:Angiotensin Receptor Antagonists / Q000008:administration & dosage*; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D005706:Gallbladder Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051379:Mice; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: D057911:Angiotensin Receptor Antagonists; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; C000705328:Ace2 protein, mouse; D000085962:Angiotensin-Converting Enzyme 2