title: Role of metformin in suppressing 1,2-dimethylhydrazine-induced colon cancer in diabetic and non-diabetic mice: effect on tumor angiogenesis and cell proliferation.
abstract: Several studies indicated that type 2 diabetes mellitus and insulin resistance are associated with increased colon cancer risk. Recently, studies suggest that metformin can reduce cancer risk in diabetic or non-diabetic patients with unclear mechanisms. This work aimed to determine the effect of metformin on chemically-induced colon cancer in mice. Colon cancer was induced using 1,2-dimethylhydrazine (DMH, 20 mg/kg/week, s.c.) for fifteen weeks. Experiment I: healthy mice were fed with basal diet for four weeks and then allocated into seven groups, (i) saline, (ii) DMH, (iii) oxaliplatin, (iv-v): metformin (100 or 200 mg/kg) and (vi-vii): oxaliplatin+metformin (100 or 200 mg/kg), respectively. Experiment II: type 2 diabetes mellitus was induced by injection of STZ (30 mg/kg) after four weeks of high-fat feeding and then mice were allocated into seven groups similar to those reported in experiment I. Examination of the colonic tissue at the end of the experiment highlighted an increase in angiogenic markers and cell proliferation and showed a greater immunostaining for insulin growth factor I receptors and CD34 in the colon of diabetic mice compared to non-diabetics. In general, metformin downregulated tumor angiogenesis and augmented the antitumor effect of oxaliplatin. Overall, the current results showed that metformin protected against DMH-induced colon cancer in non-diabetic and diabetic mice. This therapeutic effect was, at least in part, attributed to its anti-angiogenic and anti-proliferative mechanisms.
authors: Directorate of health & population, Ismailia, Egypt.
authors: Dalia K
authors: DK
authors: Zaafar
authors: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt.
authors: Sawsan A
authors: SA
authors: Zaitone
authors: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt.
authors: Yasser M
authors: YM
authors: Moustafa
mesh_terms: D019813:1,2-Dimethylhydrazine / Q000633:toxicity; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000627:therapeutic use / Q000633:toxicity; D049109:Cell Proliferation / Q000187:drug effects; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000188:drug therapy / Q000401:mortality; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D059305:Diet, High-Fat; D004359:Drug Therapy, Combination; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D008687:Metformin / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D009944:Organoplatinum Compounds / Q000627:therapeutic use / Q000633:toxicity; D000077150:Oxaliplatin; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D018952:Antigens, CD34; D000970:Antineoplastic Agents; D007004:Hypoglycemic Agents; D009944:Organoplatinum Compounds; D042461:Vascular Endothelial Growth Factor A; D000077150:Oxaliplatin; D007334:Insulin-Like Growth Factor I; D008687:Metformin; D017526:Receptor, IGF Type 1; D019813:1,2-Dimethylhydrazine