Chemopreventive effects of pioglitazone on chemically induced lung carcinogenesis in mice

Yian Wang, Michael James, Weidong Wen, Yan Lu, Eva Szabo, Ronald A. Lubet, Ming You

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

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 p53wt/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.

Original languageEnglish (US)
Pages (from-to)3074-3082
Number of pages9
JournalMolecular Cancer Therapeutics
Volume9
Issue number11
DOIs
StatePublished - Nov 2010

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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