Abstract
Metformin may help prevent the development of colorectal cancer (CRC); however, the mechanisms involved remain unclear. This study aimed to investigate the effects of metformin on CRC onset and progression in a mouse model by evaluating any changes to the intestinal mucosal barrier. Sixty BALB/C female mice were randomly divided into control, model, and low-, medium-, and high-dose treatment groups. The CRC models were induced by azoxymethane combined with dextran sulfate sodium. At the time of induction, metformin 125 mg/kg · d, 250 mg/kg · d, and 500 mg/kg · d doses were administered to the low-, medium-, and high-dose groups, respectively. After 14 weeks, no tumor was observed in the control group, and multiple tumors were observed in the four test groups. Fewer tumors emerged in the metformin groups than in the model group. The tumors in the metformin groups were smaller than those in the model group. The expression of ZO-1 and occludin in the colon tissue of mice improved after metformin intervention. We performed intervention studies with varying doses of metformin and a composite disease model (parallel induction of intestinal barrier damage and tumorigenesis) in our experimental design, allowing for novel insights into the temporal effects of metformin. Metformin can improve intestinal mucosal barrier function by restoring the expression of intestinal tight junction proteins in mice and thus may help protect against CRC within a certain dose range.