Influence of Celecoxib on Radiosensization of Irradiation￣resistant Cell Line CNE￣2R ofNasopharyngeal Carcinoma / 医药导报

ABSTRACT

Objective To investigate the effect of COX￣2 inhibitor celecoxib on radiosensitity of irradiation￣resistant cell line CNE￣2R of nasopharyngeal carcinoma and the potential mechanism. Methods Via exposing to a series of X￣ray (2, 4, 6, 8 Gy, 3 times for each dose), radio￣resistant cell subline CNE￣2R was established from human nasopharyngeal carcinoma cell CNE￣2.Radiosensitivity was detected by clone formation assay.CNE￣2R and CNE￣2 cell lines were exposed to 25, 50, 75 μmol.L-1 celecoxib, respectively.Western blotting was used to detect the protein expression of COX￣2.Clone formation assay was performed to measure the survival fraction of CNE￣2 and CNE￣2R after radiotherapy alone or radiotherapy combined with 30 μmol.L-1 celecoxib treatment.Flow cytometry was used to measure influence of radiotherapy alone or radiotherapy combined with 30 μmol.L￣1celecoxib treatment on cell apoptosis.Number of residual γ￣H2AX foci was observed by immunofluorescence assay. Results The colony forming assay demonstrated that the values of SF2, D0 , Dq , and N of CNE￣2R cell subline [(0.81±0.05), (2.15±0.07) Gy, (2.94±0.08) Gy, (3.91±0.07), respectively] was significant higher than those of CNE￣2 cell line [(0.61±0.08), (1.47±0.06) Gy, (1. 68 ± 0. 10) Gy, (3. 13 ± 0. 05), respectively]. The expression of COX￣2 protein was significantly downregulated with increasing celecoxib concentration.Surviving fraction was decreased in both CNE￣2 and CNE￣2R cell lines after irradiation.After radiotherapy combined with celecoxib, apoptosis rates of CNE￣2 and CNE￣2R cell lines [(13.10±0.63)%, (5.30±0.75)%] were higher than those of the corresponding control groups [(4.90±0.71)%, (1.82±0.82)%].Celecoxib increased radiosensitivity in nasopharyngeal carcinoma CNE￣2R and CNE￣2 cell lines.The number of residual γ￣H2AX foci after irradiation was increased by celecoxib pretreatment.The difference was statistically significant (P<0.05). Conclusion Celecoxib can enhance radiosensitivity of radio￣resistant cell subline CNE￣2R of human nasopharyngeal carcinoma in vitro.