Abstract:

Objective  To investigate the influence of celecoxib, cycloxygenase-2（COX-2） selective inhibitor, upon the proliferation of KB/VCR cells, and analyze the effect of celecoxib on the expression of P-glycoprotein（P-gp）. Methods  MTT method was employed to study the inhibitory effect of celecoxib on KB/VCR cells, which were divided into vincristine（VCR） group, Celecoxib group, Celecoxib+VCR group, Celecoxib+VCR+prostaglandin E2 （ PGE2） group. Western blot was employed to detect the expression of P-gp, Bcl-2 and Bcl-XL. Flow cytometry was used to evaluate the apoptosis of KB/VCR cells. All of the data were statistically analyzed using SPSS 13.0 software package. Results  The growth inhibition rate of KB/VCR cells in Celecoxib+VCR group was significantly higher than that in Celecoxib group, VCR group and Celecoxib+VCR+PGE2 group（P<0.01）. The expression of P-gp in Celecoxib+VCR group and Celecoxib group were markedly lower, compared with those in VCR group and Celecoxib+VCR+PGE2 group（P<0.01）. The expression of Bcl-2, Bcl-XL in Celecoxib+VCR group,  Celecoxib+VCR+PGE2 group and Celecoxib group were significantly lower than those in VCR group（P<0.01）. The apoptosis rate of Celecoxib+VCR group, Celecoxib+VCR+PGE2 group were significantly higher than those in VCR group and Celecoxib group（P<0.01）. The apoptosis rate of Celecoxib+VCR+PGE2 group were significantly lower than those in Celecoxib+VCR group（P<0.01）. Conclusion Celecoxib could enhance the toxicity of VCR against KB/VCR cells. The mechanism probably correlates with the downregulation of celecoxib on the expression of P-gp and the increase of apoptosis.

Key words:  KB/VCR cell, multidrug resistant, P-glycoprotein, cycloxygenase-2 inhibitor, apoptosis