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-X(L). 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.