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

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

Research output: Contribution to journalArticle

28 Scopus citations

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 20wk. 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.

Original languageEnglish (US)
Pages (from-to)913-921
Number of pages9
JournalMolecular Carcinogenesis
Volume50
Issue number12
DOIs
StatePublished - Dec 2011

Keywords

  • Budesonide
  • Chemoprevention
  • Lung tumorigenesis
  • Mouse
  • Pioglitazone

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

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    Fu, H., Zhang, J., Pan, J., Zhang, Q., Lu, Y., Wen, W., Lubet, R. A., Szabo, E., Chen, R., Wang, Y., Chen, D. R., & You, M. (2011). Chemoprevention of lung carcinogenesis by the combination of aerosolized budesonide and oral pioglitazone in A/J mice. Molecular Carcinogenesis, 50(12), 913-921. https://doi.org/10.1002/mc.20751