Celecoxib Inhibits Cellular Growth, Decreases Ki-67 Expression and Modifies Apoptosis in Ovarian Cancer Cell Lines
Received 20 June 2005; accepted 20 November 2005.
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 μM) 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 ≥70 μM of celecoxib for 72 and 96 h (p <0.02). All cells demonstrated pancytotoxicity at 100 μM of celecoxib. A significant decrease in Ki-67 expression in all cell lines exposed to ≥30 μM of celecoxib (p ≤0.05) for 72 h was observed. We observed significant changes in apoptosis and cleaved caspase-3 expression in SKOV3 cells exposed to 50 μM 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 expresssion. Additional studies are in progress to evaluate the effects of celecoxib on other aspects of the control of the cell cycle in cancer cells.
aDepartment of Pathology, University of Alabama at Birmingham, Birmingham, Alabama
bDepartment of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, Alabama
cHospital de Ginecología y Obstetricia, Centro Medico Nacional “La Raza,” Instituto Mexicano del Seguro Social, México City, México
Address reprint requests to: William E. Grizzle, MD, PhD, Department of Pathology, University of Alabama at Birmingham, ZRB, Room 408, 703 South 19th St., Birmingham AL 35294-007
ABSTRACT