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The Role of PPARγ in the Cyclooxygenase Pathway in Lung Cancer

Decreased expression of peroxisome proliferator activated receptor-γ (PPARγ) and high levels of the proinflammatory enzyme cyclooxygenase-2 (COX-2) have been observed in many tumor types. Both reduced (PPARγ) expression and elevated COX-2 within the tumor are associated with poor prognosis in lung c...

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Autores principales: Hazra, Saswati, Peebles, Katherine A., Sharma, Sherven, Mao, Jenny T., Dubinett, Steven M.
Formato: Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2526169/
https://www.ncbi.nlm.nih.gov/pubmed/18769553
http://dx.doi.org/10.1155/2008/790568
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author Hazra, Saswati
Peebles, Katherine A.
Sharma, Sherven
Mao, Jenny T.
Dubinett, Steven M.
author_facet Hazra, Saswati
Peebles, Katherine A.
Sharma, Sherven
Mao, Jenny T.
Dubinett, Steven M.
author_sort Hazra, Saswati
collection PubMed
description Decreased expression of peroxisome proliferator activated receptor-γ (PPARγ) and high levels of the proinflammatory enzyme cyclooxygenase-2 (COX-2) have been observed in many tumor types. Both reduced (PPARγ) expression and elevated COX-2 within the tumor are associated with poor prognosis in lung cancer patients, and recent work has indicated that these signaling pathways may be interrelated. Synthetic (PPARγ) agonists such as the thiazolidinedione (TZD) class of anti-diabetic drugs can decrease COX-2 levels, inhibit growth of non-small-cell lung cancer (NSCLC) cells in vitro, and block tumor progression in xenograft models. TZDs alter the expression of COX-2 and consequent production of the protumorigenic inflammatory molecule prostaglandin E2 (PGE2) through both (PPARγ) dependent and independent mechanisms. Certain TZDs also reduce expression of PGE2 receptors or upregulate the PGE2 catabolic enzyme 15-prostaglandin dehydrogenase. As several COX-2 enzymatic products have antitumor properties and specific COX-2 inhibition has been associated with increased risk of adverse cardiac events, directly reducing the effects or concentration of PGE2 may provide a more safe and effective strategy for lung cancer treatment. Understanding the mechanisms underlying these effects may be helpful for designing anticancer therapies. This article summarizes recent research on the relationship between (PPARγ), TZDs, and the COX-2/PGE2 pathways in lung cancer.
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spelling pubmed-25261692008-09-03 The Role of PPARγ in the Cyclooxygenase Pathway in Lung Cancer Hazra, Saswati Peebles, Katherine A. Sharma, Sherven Mao, Jenny T. Dubinett, Steven M. PPAR Res Review Article Decreased expression of peroxisome proliferator activated receptor-γ (PPARγ) and high levels of the proinflammatory enzyme cyclooxygenase-2 (COX-2) have been observed in many tumor types. Both reduced (PPARγ) expression and elevated COX-2 within the tumor are associated with poor prognosis in lung cancer patients, and recent work has indicated that these signaling pathways may be interrelated. Synthetic (PPARγ) agonists such as the thiazolidinedione (TZD) class of anti-diabetic drugs can decrease COX-2 levels, inhibit growth of non-small-cell lung cancer (NSCLC) cells in vitro, and block tumor progression in xenograft models. TZDs alter the expression of COX-2 and consequent production of the protumorigenic inflammatory molecule prostaglandin E2 (PGE2) through both (PPARγ) dependent and independent mechanisms. Certain TZDs also reduce expression of PGE2 receptors or upregulate the PGE2 catabolic enzyme 15-prostaglandin dehydrogenase. As several COX-2 enzymatic products have antitumor properties and specific COX-2 inhibition has been associated with increased risk of adverse cardiac events, directly reducing the effects or concentration of PGE2 may provide a more safe and effective strategy for lung cancer treatment. Understanding the mechanisms underlying these effects may be helpful for designing anticancer therapies. This article summarizes recent research on the relationship between (PPARγ), TZDs, and the COX-2/PGE2 pathways in lung cancer. Hindawi Publishing Corporation 2008 2008-08-27 /pmc/articles/PMC2526169/ /pubmed/18769553 http://dx.doi.org/10.1155/2008/790568 Text en Copyright © 2008 Saswati Hazra et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Article
Hazra, Saswati
Peebles, Katherine A.
Sharma, Sherven
Mao, Jenny T.
Dubinett, Steven M.
The Role of PPARγ in the Cyclooxygenase Pathway in Lung Cancer
title The Role of PPARγ in the Cyclooxygenase Pathway in Lung Cancer
title_full The Role of PPARγ in the Cyclooxygenase Pathway in Lung Cancer
title_fullStr The Role of PPARγ in the Cyclooxygenase Pathway in Lung Cancer
title_full_unstemmed The Role of PPARγ in the Cyclooxygenase Pathway in Lung Cancer
title_short The Role of PPARγ in the Cyclooxygenase Pathway in Lung Cancer
title_sort role of pparγ in the cyclooxygenase pathway in lung cancer
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2526169/
https://www.ncbi.nlm.nih.gov/pubmed/18769553
http://dx.doi.org/10.1155/2008/790568
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