Celecoxib enhances chemosensitivity of oral cancer cells by blocking cell cycle progression in vitro / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of celecoxib in enhancing the chemosensitivity of oral cancer cells and the correlation of this effect with cell cycle arrest.</p><p><b>METHODS</b>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 p21(WAF1/CIP1).</p><p><b>RESULTS</b>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 p21(WAF1/CIP1), and reduced P-gp expressions in the cells.</p><p><b>CONCLUSIONS</b>Celecoxib enhances the chemosensitivity of KB/VCR cells by down-regulating P-gp expression, which is partially mediated by modification of cyclin D1 and p21(WAF1/CIP1) to result in cell cycle arrest.</p>

Celecoxib enhances the chemotherapy sensitivity of KB/VCR cell lines to vincristine / 华西口腔医学杂志

<p><b>OBJECTIVE</b>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).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSION</b>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.</p>