Celecoxib inhibits invasion and metastasis via a cyclooxygenase 2-independent mechanism in an in vitro model of Ewing sarcoma.

Abstract

BACKGROUND/INTRODUCTION:

Previously, we reported that celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, prevented lung metastases but did not affect tumor growth in a model of Ewing sarcoma. Cyclooxygenase-2 inhibition has been proposed as an antimetastatic strategy. The mechanism of action remains unclear.

METHODS:

Ewing sarcoma cells were suspended in a soluble basement membrane extract (Cultrex; Trevigen, Inc, Gaithersburg, MD) and supplemented with celecoxib or with rofecoxib, a second COX-2 inhibitor, above a filter. Controls received solvent. After 48 hours, the cells that invaded through the basement membrane and filter were stained and counted. The assay was repeated with the addition of 500-nM prostaglandin E2 (PGE(2)).

RESULTS:

Invasion was significantly decreased in the celecoxib groups compared with the control. The addition of PGE(2) did not overcome celecoxib inhibition. Rofecoxib did not significantly affect invasion compared with control either with or without PGE(2).

CONCLUSIONS:

Celecoxib significantly inhibits invasion of Ewing sarcoma cells in vitro. Prostaglandin E2, a downstream product of COX-2, did not reverse in vitro inhibition, suggesting that celecoxib acts through a COX-2-independent mechanism. This is further supported by the failure of rofecoxib to inhibit invasion despite more selectively inhibiting COX-2.

• Authors: Meade Barlow, Morris Edelman, Richard D Glick, Bettie M Steinberg, Samuel Z Soffer
• Journal: Journal of pediatric surgery (J Pediatr Surg) Vol. 47 Issue 6 Pg. 1223-7 (Jun 2012) ISSN: 1531-5037 [Electronic] United States
• PMID: 22703797 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Cyclooxygenase 2 Inhibitors
• Lactones
• Neoplasm Proteins
• Pyrazoles
• Sulfonamides
• Sulfones
• rofecoxib
• Cyclooxygenase 2
• PTGS2 protein, human
• Celecoxib
• Dinoprostone

Topics

• Basement Membrane
• Bone Neoplasms (enzymology, pathology)
• Celecoxib
• Cell Line, Tumor (drug effects, enzymology)
• Cell Movement (drug effects)
• Cyclooxygenase 2 (physiology)
• Cyclooxygenase 2 Inhibitors (pharmacology)
• Dinoprostone (pharmacology)
• Drug Screening Assays, Antitumor
• Humans
• In Vitro Techniques
• Lactones (pharmacology)
• Neoplasm Invasiveness
• Neoplasm Metastasis
• Neoplasm Proteins (antagonists & inhibitors, physiology)
• Pyrazoles (pharmacology)
• Sarcoma, Ewing (enzymology, pathology)
• Sulfonamides (pharmacology)
• Sulfones (pharmacology)