Celecoxib enhances radiosensitivity via induction of G₂-M phase arrest and apoptosis in nasopharyngeal carcinoma.
BACKGROUND
Previous work has proposed that celecoxib may be able to enhance the effects of radiotherapy. However, the underlying mechanism of this activity has not yet been determined.


METHODS
The cell colony formation assay after the combination of celecoxib and radiation treatment was done on C666-1, CNE-1 and CNE-2 nasopharyngeal carcinoma cells, which expressed different COX-2 levels. Moreover, COX-2 knocked down or overexpressed cells were developed, and apoptosis and cell cycle analysis were performed.


RESULTS
Celecoxib enhances radiation cytotoxicity in C666-1 and CNE-1 nasopharyngeal carcinoma cells that expressed high COX-2 but not in CNE-2 cells that expressed low COX-2. The radiosensitization of celecoxib in C666-1 cells disappeared after the COX-2 knocked down, while the CNE-2 cells were radiosensitized by celecoxib after the transfection of COX-2. Moreover, celecoxib enhanced radiation-induced G2-M phase arrest was observed in some of the tested cells. Furthermore, we found that the radiosensitivity of celecoxib in nasopharyngeal carcinoma was correlated with the apoptosis induction. Additionally, the combination of celecoxib (25 mg/kg) and radiation (6 Gy) treatment significantly reduced tumor volume in C666-1 and CNE-2 nasopharyngeal carcinoma xenograft models.


CONCLUSIONS
These results indicate that the combination of celecoxib and radiation treatment has potential application in radiotherapy, and these effects may be attributable to the G2-M cell phase arrest and enhancement of cell apoptosis.
Department of Radiology, Guangdong General Hospital, Guangzhou, Guangdong, PR China.
Shui-xing
SX
Zhang
Qian-hui
QH
Qiu
Wen-bo
WB
Chen
Chang-hong
CH
Liang
Biao
B
Huang
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002277:Carcinoma; D000068579:Celecoxib; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011720:Pyrazoles / Q000494:pharmacology*; D011836:Radiation Tolerance / Q000187:drug effects*; D011838:Radiation-Sensitizing Agents / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D011720:Pyrazoles; D011838:Radiation-Sensitizing Agents; D013449:Sulfonamides; D000068579:Celecoxib