Promotion of Colon Tumors in C57BL/6J-APCmin/+ Mice by Thiazolidinedione PPARγ Agonists and a Structurally Unrelated

Thiazolidinedione PPARγ agonists (troglitazone and rosiglitazone) were previously shown to promote colon tumor formation in C57BL/6J-APCmin/+ mice, a model for human familial adenomatous polyposis. This study was conducted to determine if another thiazolidinedione PPARγ agonist, pioglitazone, and a PPARγ agonist structurally unrelated to the thiazolidinedione family, NID525, (a tetrazole-substituted phe-noxymethylquinolone), would also promote colon tumors in this mouse model. Mice were treated in-feed with the thiazolidinediones troglitazone (150 mg/kg/day), rosiglitazone (20 mg/kg/day), or pioglitazone (150 mg/kg/day), or with NID525 (150 mg/kg/day) for 8 weeks. An increased inci-dence in colon tumors compared to controls was observed for all of the thiazolidinedione-treated groups as well as the NID525-treated group. These results indicate that the tumor-promoting effect of PPARγ agonists in the colon of C57BL/6J-APCmin/+ mice is likely related to the pharmacological activity of this group of drugs and not the thiazolidinedione structure. Keywords. Thiazolidinedione; PPAR gamma agonist; colon tumors; APC min mouse; adenomatous polyposis coli gene