title: Angiotensin-converting enzyme 2 acts as a potential molecular target for pancreatic cancer therapy.
abstract: Angiotensin-converting enzyme 2 (ACE2) is a novel component of the renin-angiotensin system that could counterbalance the growth-promoting function of angiotensin-converting enzyme (ACE). Our previous results have shown that ACE2 is lowly expressed in pancreas, and widely down-regulated in pancreatic cancer tissues and cells. In the present study, we investigated the effect of restoration of ACE2 expression on the growth of pancreatic cancer. We found that restoration of ACE2 protein suppressed cell proliferation, motility and increased the sensitivity to hypoxia induced injury in BxPC3 and SW1990 cell lines. Stably transfected cells overexpressing ACE2 exhibited decreased tumorigenicity and delayed tumor growth, both in vitro and in vivo. In addition, restoration of ACE2 expression mediated by adenovirus vector significantly inhibited the established tumor growth, strongly enhanced the anti-tumor activity of gemcitabine in a pancreatic cancer xenograft model in vivo, and significantly prolonged the survival time of animals bearing tumor xenografts. These results provide evidence that ACE2 plays a pivotal role in the development of pancreatic cancer, and suggest that ACE2 is a promising candidate for pancreatic cancer treatment.
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital, Zhengzhou University School of Medicine, Zhengzhou 450052, China; Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, No. 197, Ruijin Er Road, Shanghai 200025, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Respiratory Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China.
authors.forename: Ruifeng
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital, Zhengzhou University School of Medicine, Zhengzhou 450052, China.
authors.forename: Lianfeng
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, No. 197, Ruijin Er Road, Shanghai 200025, China.
authors.forename: Weiyan
authors.initials: W
authors.lastname: Yao
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital, Zhengzhou University School of Medicine, Zhengzhou 450052, China.
authors.forename: Jiansheng
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, No. 197, Ruijin Er Road, Shanghai 200025, China. Electronic address: yyz28@medmail.com.cn.
authors.forename: Yaozong
authors.initials: Y
authors.lastname: Yuan
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D015153:Blotting, Western; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D003114:Colony-Forming Units Assay; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D005260:Female; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage; D006801:Humans; D000860:Hypoxia; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000473:pathology / Q000628:therapy*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D012333:RNA, Messenger; D003841:Deoxycytidine; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; C000705328:Ace2 protein, mouse; D000085962:Angiotensin-Converting Enzyme 2; D000093542:Gemcitabine