Celecoxib enhances chemosensitivity of oral cancer cells by blocking cell cycle progression in vitro.
- Author:
Wenxiao LIAO
1
;
Yixuan YAN
;
Yanqing HUANG
;
Weizhong LI
Author Information
- Publication Type:Journal Article
- MeSH: ATP-Binding Cassette, Sub-Family B, Member 1; metabolism; Celecoxib; Cell Cycle; drug effects; Cell Line, Tumor; Cyclin D1; metabolism; Cyclin-Dependent Kinase Inhibitor p21; metabolism; Drug Resistance, Neoplasm; drug effects; Humans; KB Cells; Mouth Neoplasms; drug therapy; metabolism; Pyrazoles; pharmacology; Sulfonamides; pharmacology
- From: Journal of Southern Medical University 2013;33(6):885-888
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the effect of celecoxib in enhancing the chemosensitivity of oral cancer cells and the correlation of this effect with cell cycle arrest.
METHODSKB/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).
RESULTSLow 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.
CONCLUSIONSCelecoxib 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.