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Prostaglandins Leukot Essent Fatty Acids. 2007 Jul;77(1):51-8. Epub 2007 Aug 13.

Ciglitazone mediates COX-2 dependent suppression of PGE2 in human non-small cell lung cancer cells.

Author information

1
Lung Cancer Research Program of the Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. Shazra@mednet.ucla.edu

Abstract

BACKGROUND:

Cyclooxygenase-2 (COX-2) over-expression and subsequent prostaglandin E2 (PGE2) production are frequently associated with human non-small-cell lung cancer (NSCLC) and are involved in tumor proliferation, invasion, angiogenesis, and resistance to apoptosis. Here, we report that ciglitazone downregulates PGE2 in NSCLC cells.

METHODS:

PGE2 ELISA assay and COX-2 ELISA assay were performed for measuring PGE2 and COX-2, respectively, in NSCLC. The mRNA level of COX-2 was measured by semi-quantitative RT-PCR. The transient transfection experiments were performed to measure COX-2 and peroxisome proliferator-response element (PPRE) promoter activity in NSCLC. Western blots were unitized to measure PGE synthase (PGES) and 15-hydroxyprostaglandin dehydrogenase (15-PGDH) protein expression.

RESULTS:

COX-2 ELISA assays suggested that ciglitazone-dependent inhibition of PGE2 occurs through the suppression of COX-2. Ciglitazone treatment suppressed COX-2 mRNA expression and COX-2 promoter activity while upregulating PPRE promoter activity. Ciglitazone did not modify the expression of enzymes downstream of COX-2 including PGES and 15-PGDH. Utilization of a dominant-negative PPARgamma showed that the suppression of COX-2 and PGE2 by ciglitazone is mediated via non-PPAR pathways.

CONCLUSION:

Taken together, our findings suggest that ciglitazone is a negative modulator of COX-2/PGE2 in NSCLC.

PMID:
17697767
PMCID:
PMC2045645
DOI:
10.1016/j.plefa.2007.05.006
[Indexed for MEDLINE]
Free PMC Article

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