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Resveratrol Phenocopies the Suppressive Effects of Insulin‐like Growth Factor Receptor‐1 siRNA on IGF‐1 Promoted Colon Cancer Cell Proliferation

The insulin‐like growth factor (IGF) system is believed to mediate obesity‐related increase in the risk of colon cancer. IGFs activate the β‐catenin pathway, which plays a central role in the growth of colon cancer cells. Dietary resveratrol exerts inhibitory effects on cancers; however, its molecular mechanisms are not fully elucidated, particularly in relation to obesity‐promoted cancers. We hypothesized that resveratrol suppresses colon cancer cell proliferation by inhibiting activation of IGF receptor‐1 (IGF‐1R) in response to IGFs (elevated during obesity). IGF‐1 (10 nM) promoted proliferation of colon cancer cells, in vitro, as expected. Resveratrol (50–150 μM) or IGF‐1R siRNA (100 nM) inhibited (p < 0.05) proliferation of colon cancer cells in response to both exogenous and autocrine IGFs. The relative levels of IGF‐1R were reduced (p < 0.05) in cells treated with either resveratrol or IGF‐1R siRNA, in association with a loss (p < 0.05) in Akt activation, GSK3β phosphorylation, and cyclin D1 levels. These results suggest that resveratrol effectively phenocopies the inhibitory properties of IGF‐1R siRNA and may thus be a potent chemopreventive/therapeutic agent against obesity‐associated increase in colon cancer risk. We will examine this possibility in future studies using in vivo models. Funded by TAES and AICR 058094.