Pioglitazone is a PPARγ agonist commonly prescribed for the clinical treatment of diabetes. We sought to expand its use to lung cancer prevention in a benzo[a]pyrene (B[a]P) mouse model with direct lung delivery via inhalation. Initially we conducted inhalational toxicity experiments with 0, 15, 50, 150, and 450 μg/kg body weight/day pioglitazone in 40 A/J mice. We examined the animals for any physical toxicity and bronchoalveolar lavage fluids for inflammatory and cytotoxicity markers. Doses up to and including 450 μg/kg bw/day failed to demonstrate toxicity with aerosol pioglitazone. For chemoprevention experiments, A/J mice were randomized to treatment groups of inhaled doses of 0, 50, 150, or 450 µg/kg bw/day pioglitazone one week or eight weeks after the last dose of B[a]P. For the early treatment group we found up to 32% decrease in lung adenoma formation with 450 µg/kg bw/day pioglitazone. We repeated the treatments in a second late stage experiment and found up to 44% decreases in lung adenoma formation in doses of pioglitazone of 150 µg/kg bw/day and 450 µg/kg bw/day. Both the early and the late stage experiment demonstrated biologically relevant and statistically significant decreases in adenoma formation. We conclude aerosol pioglitazone is well tolerated in the A/J mouse model and a promising chemoprevention agent for the lower respiratory tract.
- Received July 1, 2016.
- Revision received November 9, 2016.
- Accepted November 28, 2016.
- Copyright ©2016, American Association for Cancer Research.