Promotion of Colon Tumors in C57BL/6J-APC super(min)/+ Mice by Thiazolidinedione PPARn Agonists and a Structurally Unrelated PPARn Agonist

Thiazolidinedione PPARn agonists (troglitazone and rosiglitazone) were previously shown to promote colon tumor formation in C57BL/6J-APC super(min)/+ mice, a model for human familial adenomatous polyposis. This study was conducted to determine if another thiazolidinedione PPARn agonist, pioglitazone, and a PPARn agonist structurally unrelated to the thiazolidinedione family, NID525, (a tetrazole-substituted phenoxymethylquinolone), 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 incidence 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 PPARn agonists in the colon of C57BL/6J-APC super(min)/+ mice is likely related to the pharmacological activity of this group of drugs and not the thiazolidinedione structure.