title: Exenatide suppresses 1,2-dimethylhydrazine-induced colon cancer in diabetic mice: Effect on tumor angiogenesis and cell proliferation.
abstract: Colon cancer is the third leading cause of cancer mortality worldwide, which results from interactions of different factors. It is frequently a pathological consequence of persistent inflammation. Diabetes affects several cancers and is positively correlated with the incidence of colon cancer. This study aimed to study the effect of exenatide in ameliorating inflammation, angiogenesis and cell proliferation in 1,2-dimethyl hydrazine (DMH) induced colorectal carcinoma in diabetic mice. Mice were randomly allocated into six groups, 8 mice each. Group 1: vehicle control group. Group 2: diabetic control group. Group 3: DMH control group: diabetic mice treated with DMH (20mg/kg/week,s.c.) for 15 week. Group 4: DMH-cisplatin group: mice received cisplatin (4mg/kg/week, i.p.). Groups 5 & 6: DMH-exenatide (10 and 20μg/kg) group: mice received exenatide (10 or 20μg/kg/day,s.c.), respectively. The present results highlighted an increase in angiogenic markers and cell proliferation in the DMH-diabetic group in comparison with the control group with greater expression of endothelial marker (CD34) and Ki-67 in colon tissue. Monotherapy with cisplatin or exenatide (10 and 20μg/kg) downregulated these markers to different extents. The current results provided evidence that exenatide represents a promising chemopreventive effect against DMH-induced colon carcinogenesis in diabetic mice, at least in part, attributed to its anti-angiogenic and anti-proliferative mechanisms.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt. Electronic address: dmon_kamal@yahoo.com.
authors.forename: Mona K
authors.initials: MK
authors.lastname: Tawfik
authors.affiliation: Department of Physiology, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt.
authors.forename: Magda I
authors.initials: MI
authors.lastname: Mohamed
mesh_terms: D019813:1,2-Dimethylhydrazine; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use; D003106:Colon / Q000187:drug effects / Q000473:pathology; D003110:Colonic Neoplasms / Q000097:blood / Q000098:blood supply* / Q000139:chemically induced / Q000188:drug therapy*; D051546:Cyclooxygenase 2 / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D000077270:Exenatide; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D015850:Interleukin-6 / Q000097:blood; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D051379:Mice; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000473:pathology; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D014688:Venoms / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D018952:Antigens, CD34; D015850:Interleukin-6; D019394:Ki-67 Antigen; D010455:Peptides; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D014688:Venoms; D000077270:Exenatide; D051546:Cyclooxygenase 2; D040301:Vascular Endothelial Growth Factor Receptor-2; D019813:1,2-Dimethylhydrazine; D002945:Cisplatin
keywords: Angiogenesis; Cell proliferation; Colonic neoplasm; Diabetes mellitus; Exenatide; Inflammation