Celecoxib inhibits cellular growth, decreases Ki-67 expression and modifies apoptosis in ovarian cancer cell lines.

Abstract

BACKGROUND:

There is controversy on the safety of inhibitors of cyclooxygenase administered at high doses; however, these drugs have been reported to be effective in the prevention of a variety of human cancers. To determine if celecoxib influences cellular growth, we evaluated several effects in ovarian carcinoma cell lines.

METHODS:

CAOV3, OVCAR3 and SKOV3 cell lines were exposed to different concentrations of celecoxib (0-100 microM) for 24-96 h. Cellular growth was assessed using a cell viability assay. Immunohistochemistry was performed to evaluate Ki-67 and cleaved caspase-3. Apoptosis was determined by a TUNEL assay, and Western blot was used to determine COX-2 protein expression.

RESULTS:

We observed a significant decrease in the cellular growth of all cell lines studied exposed to > or = 70 microM of celecoxib for 72 and 96 h (p < 0.02). All cells demonstrated pancytotoxicity at 100 microM of celecoxib. A significant decrease in Ki-67 expression in all cell lines exposed to > or = 30 microM of celecoxib (p < or = 0.05) for 72 h was observed. We observed significant changes in apoptosis and cleaved caspase-3 expression in SKOV3 cells exposed to 50 microM of celecoxib. Downregulation of COX-2 protein expression caused by celecoxib was observed in SKOV3 cells.

CONCLUSIONS:

We found that celecoxib inhibits cellular growth and proliferation in a dose-dependent manner in all cell lines studied. SKOV3 cells showed an increase in cleaved caspase-3 expression. Additional studies are in progress to evaluate the effects of celecoxib on other aspects of the control of the cell cycle in cancer cells.

• Authors: Víctor Vital-Reyes, Cristina Rodríguez-Burford, David C Chhieng, Denise K Oelschlager, Alejandro Reyes-Fuentes, Mack Barnes, William E Grizzle
• Journal: Archives of medical research (Arch Med Res) Vol. 37 Issue 6 Pg. 689-95 (Aug 2006) ISSN: 0188-4409 [Print] United States
• PMID: 16824926 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Cyclooxygenase 2 Inhibitors
• Ki-67 Antigen
• Pyrazoles
• Sulfonamides
• Cyclooxygenase 2
• Caspase 3
• Celecoxib

Topics

• Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
• Apoptosis (drug effects)
• Caspase 3 (metabolism)
• Celecoxib
• Cell Growth Processes (drug effects)
• Cell Line, Tumor (drug effects)
• Cyclooxygenase 2 (metabolism)
• Cyclooxygenase 2 Inhibitors (pharmacology)
• Dose-Response Relationship, Drug
• Female
• Humans
• In Situ Nick-End Labeling
• Ki-67 Antigen (metabolism)
• Ovarian Neoplasms (metabolism)
• Pyrazoles (pharmacology)
• Sulfonamides (pharmacology)