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.
Highlights
Cancer is a class of diseases characterized by out-of-control cell growth
Diabetic mice treated with metformin (100 or 200 mg/kg) as well as the combination 1 group showed a significant increase in serum insulin-like growth factor-I (IGF-I) level compared to diabetic/DMH group (Table 2)
Colon of diabetic/DMH mice treated with oxaliplatin showing inactive lining epithelium with flattened nuclei and a few inflammatory cells infiltration in between 680
Summary
Cancer is a class of diseases characterized by out-of-control cell growth. Colorectal cancer is the third most commonly diagnosed cancer in males and the second in females. Colorectal cancer is the second leading cause of cancer death in developed countries [1]. Type 2 diabetes mellitus has been linked to the increased risk of cancer [2]. Higher rates of hepatic [3], colon [4] and endometrial [5] cancer. A meta-analysis was conducted of published data on the association between diabetes and the incidence as well as mortality of colorectal cancer [4]. The factors underlying the increased risk has been postulated but never completely elucidated in the medical literature
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