Suppression of intestinal polyp development in Apc(Min/+) mice through inhibition of P-glycoprotein using verapamil

P-glycoprotein (P-gp; encoded by the Mdr1a gene) is known to be associated with colon tumorigenesis through transcriptional activation and/or epigenetic modification. We investigated whether inhibition of P-gp function might decrease intestinal tumorigenesis. We used verapamil as an inhibitor of P-gp function in Apc(Min/+) mice, which lack a functional Apc gene product. We determined the number of intestinal polyps and 1-year survival rates after the ingestion of 10, 25, and 50 mg/kg/day verapamil contained in dry pellets. The number of polyps in Mdr1a(+/+)Apc(Min/+) mice fed with pellets containing verapamil was significantly lower than that in mice fed with verapamil-free pellets. The 1-year survival rate of verapamil-fed mice was also improved in a dose-dependent manner. These results were similar to data from P-gp knockout mice. These results indicated that it might be possible to use verapamil to inhibit polyp development during the early stage of colon carcinogenesis. Thus, we propose a novel chemopreventive agent for colorectal cancer that acts by inhibiting P-gp function.