Chemoprevention of lung carcinogenesis by the combination of aerosolized budesonide and oral pioglitazone in A/J mice. Mol Carcinog 2011 Dec;50(12):913-21
Date
03/05/2011Pubmed ID
21374736Pubmed Central ID
PMC6015734DOI
10.1002/mc.20751Scopus ID
2-s2.0-80155129711 (requires institutional sign-in at Scopus site) 40 CitationsAbstract
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.
Author List
Fu H, Zhang J, Pan J, Zhang Q, Lu Y, Wen W, Lubet RA, Szabo E, Chen R, Wang Y, Chen DR, You MMESH terms used to index this publication - Major topics in bold
AnimalsAntineoplastic Combined Chemotherapy Protocols
Benzo(a)pyrene
Budesonide
Carcinogens
Cell Line, Tumor
Cell Proliferation
Cell Transformation, Neoplastic
Chemoprevention
Female
Glucocorticoids
Humans
Lung
Lung Neoplasms
Mice
Mice, Inbred A
Thiazolidinediones
