Involvement of IGF/IGFBP/Erk axis in the exercise-mediated preventive effects on colorectal cancer in rats

Recent studies have indicated that downregulation of insulin-like growth factor (IGF)-1 and its downstream targets are the main mechanisms underlying the anti-cancer impact of exercise. Therefore, we examined the impact of exercise on chemically induced-aberrant crypt foci (ACF), the earliest step of colorectal carcinogenesis, in rats and involvement of the IGF-1/IGF binding protein (IGFBP)-3/Erk axis. Twenty-four male Wistar rats were assigned into two groups (n=12): the control and exercise group. After eight weeks of training intervention, 6 rats were randomly selected from each group and received four injections of 1,2-dimethylhydrazine (DMH; 40 mg/kg), for two weeks. 0.2% methylene blue staining was used to evaluate the number of ACF in the colon. IGF-1 and IGFBP-3 protein levels in the serum were measured using commercially available ELISA kits for rat. The expression levels of proliferating cell nuclear antigen (PCNA), Erk1/2 and p-Erk1/2 were evaluated in colon tissue. Histological assessments were also performed in all groups. We found that the total number of ACF was significantly lowered after eight-week exercise (P<0.05). Moreover, the exercise program downregulated the IGF-1, PCNA, and p-Erk1/2 expressions and upregulated IGFBP-3 expression. Exercise was also found to increase the goblet cell number and improved colon architecture. Our finding demonstrated reduced ACF number in rat colons following exercise training, and this function may be associated with the inhibition of IGF-1/IGFBP-3/Erk1/2 signaling. Therefore, exercise appears to result in a lower number of ACF for preventing colon cancer.