reclinical Development Cancer herapeutics hemopreventive Effects of Pioglitazone on Chemically T e duced Lung Carcinogenesis in Mic

Downloa Pioglitazone [(RS)-5-(4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl)thiazolidine-2,4-dione] is a ligand of nuclear ceptor peroxisome proliferator-activated receptor γ that is approved for the treatment of type II diabetes ellitus. Activation of peroxisome proliferator-activated receptor γ has been associated with anticancer tivities in a variety of cancer cell lines through inhibition of proliferation and promotion of apoptosis. e examined the effect of pioglitazone on lung cancer development in carcinogen-induced lung adenocarcima and squamous cell carcinoma (SCC). When pioglitazone was administered beginning 8 weeks after the st carcinogen treatment when microscopic adenomas already existed, pioglitazone significantly inhibited mor load (sum of tumor volume per lung in average) by 64% (P < 0.05) in p53 mice and 50% (P < 0.05) p53 mice in the lung adenocarcinoma model. Delayed administration of pioglitazone caused a ited (35%, P < 0.05) decrease in lung SCC. Induction of apoptosis occurred in both model systems. These ta show that pioglitazone significantly inhibited progression of both adenocarcinoma and SCC in the two mouse model systems. Mol Cancer Ther; 9(11); 3074–82. ©2010 AACR.