Journal Article

Rosiglitazone prevents the progression of preinvasive lung cancer in a murine model

Christopher M. Lyon, Donna M. Klinge, Kieu C. Do, Marcie J. Grimes, Cindy L. Thomas, Leah A. Damiani, Thomas H. March, Christine A. Stidley and Steven A. Belinsky

in Carcinogenesis

Volume 30, issue 12, pages 2095-2099
Published in print December 2009 | ISSN: 0143-3334
Published online October 2009 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgp260
Rosiglitazone prevents the progression of preinvasive lung cancer in a murine model

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There is a critical need to identify efficacious chemopreventive agents for lung cancer that can be taken chronically with no side effects and whose mechanisms of action do not involve genotoxicity that could drive, rather than impede, cancer progression. We evaluated the ability of a chemopreventive cocktail that included selenium (antioxidant), rosiglitazone (peroxisome proliferator-activated receptor gamma agonist), sodium phenylbutyrate or valproic acid (histone deacetylase inhibitors) and hydralazine (cytosine-demethylating agent) to prevent the progression of lung cancer in A/J mice treated with NNK. Agents were administered alone or in various combinations. Effects of the chemopreventive agents were quantified based on the proportion of hyperplasias and adenomas within the mouse lung. Significant effects on tumor progression were seen in all treatment groups that included rosiglitazone as reflected by a 47–57% increase in number of hyperplasias and a 10–30% decrease in adenomas. Cell proliferation was also reduced in these treatment groups by ∼40%. Interestingly, while treatment with rosiglitazone alone did not significantly affect lesion size, striking effects were seen in the combination therapy group that included sodium phenylbutyrate, with the volume of hyperplasias and adenomas decreasing by 40 and 77%, respectively. These studies demonstrate for the first time that chronic in vivo administration of rosiglitazone, used in the management of diabetes mellitus, can significantly block the progression of premalignant lung cancer in the A/J mouse model.

Journal Article.  4251 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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