Abstract
Metformin is a biguanide derivative that has been widely used for diabetic treatment. Previously, we reported the chemopreventive effect of metformin in two rodent models of colorectal carcinogenesis. However, besides epidemiologic studies, little is known about the effects of metformin on human colorectal carcinogenesis. The objective of this pilot study was to evaluate the chemopreventive effects of metformin on rectal aberrant crypt foci (ACF), which are the endoscopic surrogate marker of colorectal cancer. We prospectively randomized 30 non-diabetic patients with ACF to treatment with metformin (250 mg/day; n = 15) or no treatment (control; n = 15); 27 patients were evaluable for endpoint analyses (12 metformin; 15 control); the two groups were similar in ACF number and other baseline clinical characteristics. Magnifying colonoscopy determined the number of rectal ACF in each patient at baseline and after 1 month in a blinded fashion (as were all laboratory-endpoint analyses). In addition, the proliferative activity of the colonic epithelium was examined by determining the proliferating cell nuclear antigen labeling index, and the apoptotic activity by terminal deoxynucleotidyl transferase dUTP nick end labeling. At 1 month, significant decrease in the mean number of ACF per person was observed in the metformin group (8.54 ± 6.37 before treatment versus 5.32 ± 4.87 at 1 month; P = 0.009), whereas in the control group the mean number of ACF did not change significantly. The proliferating cell nuclear antigen index was significantly decreased and the apoptotic cell index remained unaltered in normal rectal epithelium in metformin patients. The present study demonstrated that metformin has the potential to suppress colonic epithelial proliferation and rectal ACF formation in humans, suggesting that its promise for the chemoprevention of colorectal cancer.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):B53.
RSS Feeds