title: Angiotensin II promotes the progression of human gastric cancer.
abstract: The renin-angiotensin system (RAS) plays an important role in cardiovascular homeostasis, carcinogenesis‑related angiogenesis and cell proliferation. The present study was undertaken to determine the expression of angiotensin (Ang) II, Ang II type 1 and 2 receptors (AT1R and AT2R), and the activity of the angiotensin‑converting enzyme (ACE) in gastric cancer tissue. The study further examined the roles of Ang II in the growth of gastric cancer cells in nude mice and in the migration and proliferation of MKN45 human gastric cancer cells. Gastric cancer tissue samples were obtained from gastric cancer patients. The levels of Ang II, AT1R and AT2R, as well as ACE activity were increased in tissues from gastric cancer patients compared to healthy tissues. A gastric cancer model was established by intraperitoneally injecting MKN45 human gastric cancer cells in nude mice, intraperitoneally injecting Ang II and measuring the tumor size every two days. Ang II treatment caused an increase in the size and weight of the tumor mass in nude mice, whereas the AT1R antagonist losartan significantly inhibited the size and weight of the tumor. While Ang II enhanced the migratory and proliferative rate of MKN45 human gastric cancer cells, these were significantly reduced following treatment with losartan. These results indicate that RAS is activated in gastric cancer patients and Ang II promotes the progression of gastric cancer in nude mice, as well as the migration and proliferation of MKN45 human gastric cancer cells.
authors.affiliation: Department of Gerontics, Drum Tower Hospital, College of Medicine, Nanjing University, Nanjing, Jiangsu 210008, P.R. China.
authors.forename: Ming-Min
authors.initials: MM
authors.lastname: Huang
authors.affiliation: Department of Gerontics, Drum Tower Hospital, College of Medicine, Nanjing University, Nanjing, Jiangsu 210008, P.R. China.
authors.forename: Ai-Bin
authors.initials: AB
authors.lastname: Guo
authors.affiliation: Department of Surgical Oncology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Jun-Feng
authors.initials: JF
authors.lastname: Sun
authors.affiliation: Department of Gerontics, Drum Tower Hospital, College of Medicine, Nanjing University, Nanjing, Jiangsu 210008, P.R. China.
authors.forename: Xiao-Lin
authors.initials: XL
authors.lastname: Chen
authors.affiliation: Department of Gerontics, Drum Tower Hospital, College of Medicine, Nanjing University, Nanjing, Jiangsu 210008, P.R. China.
authors.forename: Zhen-Yu
authors.initials: ZY
authors.lastname: Yin
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018450:Disease Progression; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D019808:Losartan / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000737:chemistry / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D014183:Transplantation, Heterologous
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A; D019808:Losartan