In:
Cancer Prevention Research, American Association for Cancer Research (AACR), Vol. 10, No. 2 ( 2017-02-01), p. 124-132
Abstract:
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/d 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/d pioglitazone 1 or 8 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/d 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 and 450 μg/kg bw/day. Both the early- and the late-stage experi ments demonstrated biologically relevant and statistically significant decreases in adenoma formation. We conclude that aerosol pioglitazone is well-tolerated in the A/J mouse model and a promising chemoprevention agent for the lower respiratory tract. Cancer Prev Res; 10(2); 124–32. ©2016 AACR.
Type of Medium:
Online Resource
ISSN:
1940-6207
,
1940-6215
DOI:
10.1158/1940-6207.CAPR-16-0174
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2017
detail.hit.zdb_id:
2422346-3