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Chemoprevention of lung carcinogenesis by the combination of aerosolized budesonide and oral pioglitazone in A/J mice

✍ Scribed by Huijing Fu; Jingjie Zhang; Jing Pan; Qi Zhang; Yan Lu; Weidong Wen; Ronald A. Lubet; Eva Szabo; Ruth Chen; Yian Wang; Da-Ren Chen; Ming You

Publisher: John Wiley and Sons
Year: 2011
Tongue: English
Weight: 248 KB
Volume: 50
Category: Article
ISSN: 0899-1987
DOI: 10.1002/mc.20751

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✦ Synopsis

Abstract

Budesonide, a synthetic glucocorticoid used for treating asthma, and pioglitazone, a synthetic peroxisome proliferator‐activated receptors γ ligand used for the treatment of diabetes, were evaluated for their combinational chemopreventive efficacy on mouse lung cancer using female A/J mice with benzo(a)pyrene used as the carcinogen. All chemopreventive treatments began 2‐wk post‐carcinogen treatment and continued daily for 20 wk. Budesonide was administered by the aerosol route using an improved aerosol delivery system. Pioglitazone was introduced by oral gavage. The characterization of drug distribution showed that budesonide introduced by aerosol delivery accumulated only in the lung. Budesonide alone reduced tumor load by 78% and pioglitazone alone reduced tumor load by 63%. By combining aerosolized budesonide with pioglitazone, the inhibition on tumor load was 90%. In vitro experiments using human cancer cells showed that budesonide and pioglitazone exhibited independent, additive inhibitory effects on cell growth. Our results provide evidence that aerosolized budesonide and oral pioglitazone could be a promising drug combination for lung cancer chemoprevention. © 2011 Wiley Periodicals, Inc.

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