LI Wenwen, SUN Wei, LUO Min, HUANG Yu, ZHANG Linli, HU Guoqing
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-1 celecoxib 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.