Abstract: Objective To investigate the effect of celecoxib in enhancing the chemosensitivity of oral cancer cells and the
correlation of this effect with cell cycle arrest. Methods KB/VCR cell line was treated with celecoxib (10, 20, 40, and 80 μmol/L)
and/or VCR (0.375, 0.75, 1.5, and 3 μmol/L), and the growth inhibition rates of KB/VCR cells were assessed with MTT assay.
Flow cytometry was employed to analyze the distribution of cell cycle. Western blotting was performed to detect the
expression of P-glycoprotein (P-gp) and the cell cycle related proteins Cyclin D1 and p21WAF1/CIP1. Results Low concentrations of
celecoxib (<20 μmol/L) produced no obvious effect on the proliferation of the cells. But at 10 μmol/L, celecoxib significantly
enhanced the toxicity of VCR in a time-dependent manner, and the combined treatments for 24, 48, and 72 h caused growth
inhibition rates of (37.53 ± 2.05)% , (46.67 ± 3.17)% and (54.02 ± 1.53)% , respectively, significantly higher than those following
treatments with celecoxib or VCR alone (P<0.01). Compared with the cells treated with VCR alone , the cells with combined
treatments showed a significantly increased cell percentage in G0/G1 phase［(56.08 ± 0.46)%］with decrease percentages in S
phase［(22.83±0.20)%］and G2/M phase［(21.09%±0.66)%］. The combined treatment also significantly down-regulated cyclin
D1, up-regulated p21WAF1/CIP1, and reduced P-gp expressions in the cells. Conclusions Celecoxib enhances the chemosensitivity
of KB/VCR cells by down-regulating P-gp expression, which is partially mediated by modification of cyclin D1 and p21WAF1/CIP1
to result in cell cycle arrest.