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Chemopreventive effects of pioglitazone on chemically induced lung carcinogenesis in mice. Mol Cancer Ther 2010 Nov;9(11):3074-82 PMID: 21045137

Pubmed ID

21045137

DOI

10.1158/1535-7163.MCT-10-0510

Abstract

Pioglitazone [(RS)-5-(4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl)thiazolidine-2,4-dione] is a ligand of nuclear receptor peroxisome proliferator-activated receptor γ that is approved for the treatment of type II diabetes mellitus. Activation of peroxisome proliferator-activated receptor γ has been associated with anticancer activities in a variety of cancer cell lines through inhibition of proliferation and promotion of apoptosis. We examined the effect of pioglitazone on lung cancer development in carcinogen-induced lung adenocarcinoma and squamous cell carcinoma (SCC). When pioglitazone was administered beginning 8 weeks after the first carcinogen treatment when microscopic adenomas already existed, pioglitazone significantly inhibited tumor load (sum of tumor volume per lung in average) by 64% (P < 0.05) in p53(wt/wt) mice and 50% (P < 0.05) in p53(wt/Ala135Val) mice in the lung adenocarcinoma model. Delayed administration of pioglitazone caused a limited (35%, P < 0.05) decrease in lung SCC. Induction of apoptosis occurred in both model systems. These data show that pioglitazone significantly inhibited progression of both adenocarcinoma and SCC in the two mouse model systems.

Author List

Wang Y, James M, Wen W, Lu Y, Szabo E, Lubet RA, You M

Authors

Michael James PhD Assistant Professor in the Surgery department at Medical College of Wisconsin
Yian Wang MD, PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
Ming You MD, PhD Associate Provost, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin




Scopus

2-s2.0-78649668811   39 Citations

MESH terms used to index this publication - Major topics in bold

Adenocarcinoma
Animals
Antineoplastic Agents
Carcinogens
Carcinoma, Squamous Cell
Chemoprevention
Cytoprotection
Drug Evaluation, Preclinical
Female
Humans
Lung Neoplasms
Mice
Mice, Transgenic
Thiazolidinediones
Tumor Cells, Cultured
Urethane
jenkins-FCD Prod-353 9ccd8489072cb19f5b9f808bb23ed672c582f41e