Celecoxib induces apoptosis and cell-cycle arrest in nasopharyngeal carcinoma cell lines via inhibition of STAT3 phosphorylation  

作　　者：Dong-bo LIU Guang-yuan HU Guo-xian LONG Hong QIU Qi MEI Guo-qing HU 

机构地区：[1]Cancer Center,Tongii Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China

出　　处：《Acta Pharmacologica Sinica》2012年第5期682-690,共9页中国药理学报（英文版）

基　　金：Acknowledgements We thank Prof Ya CAO at the Cancer Research Institute of Central South University for his gift of the HNE1 and CNE1- LMP1 cell lines. This project was supported by a grant from the National Natural Science Foundation of China （No 30470525）,

摘　　要：Aim： To investigate the mechanisms underlying the anticancer effect of celecoxib on nasopharyngeal carcinoma （NPC）. Methods： NPC cell lines, HNE1 and CNE1-LMP1, were treated with various concentrations of celecoxib for 48 h. The antiproliferative effect of celecoxib was assessed using MTT assay. Both cell cycle profiles and apoptosis were analyzed using flow cytometry. Western blot was used to measure the levels of signal transducer and activator of transcription 3 （STAT3）, phosphorylated STAT3^Y705 （pSTAT3^Y705）, COX-2, Survivin, Mcl-1, Bcl-2 and Cyclin DI. Results： Celecoxib （10-75 pmol/L） inhibited the proliferation of the NPC cell lines in a dose-dependent manner. Celecoxib （25 and 50 pmol/L） induced apoptosis and cell-cycle arrest at the Go/G1 checkpoint in the NPC cell lines, which was associated with significantly reduced STAT3 phosphorylation. The genes downstream of STAT3 （ie, Survivin, Mcl-1, Bcl-2 and Cyclin D1） were significantly down-regulated after exposure to celecoxib （25 and 50 pmol/L）. Conclusion： The anticancer effects of celecoxib on NPC cell lines results from inducing apoptosis and cell cycle arrest, which may be partly mediated through the STAT3 pathway.Aim： To investigate the mechanisms underlying the anticancer effect of celecoxib on nasopharyngeal carcinoma （NPC）. Methods： NPC cell lines, HNE1 and CNE1-LMP1, were treated with various concentrations of celecoxib for 48 h. The antiproliferative effect of celecoxib was assessed using MTT assay. Both cell cycle profiles and apoptosis were analyzed using flow cytometry. Western blot was used to measure the levels of signal transducer and activator of transcription 3 （STAT3）, phosphorylated STAT3^Y705 （pSTAT3^Y705）, COX-2, Survivin, Mcl-1, Bcl-2 and Cyclin DI. Results： Celecoxib （10-75 pmol/L） inhibited the proliferation of the NPC cell lines in a dose-dependent manner. Celecoxib （25 and 50 pmol/L） induced apoptosis and cell-cycle arrest at the Go/G1 checkpoint in the NPC cell lines, which was associated with significantly reduced STAT3 phosphorylation. The genes downstream of STAT3 （ie, Survivin, Mcl-1, Bcl-2 and Cyclin D1） were significantly down-regulated after exposure to celecoxib （25 and 50 pmol/L）. Conclusion： The anticancer effects of celecoxib on NPC cell lines results from inducing apoptosis and cell cycle arrest, which may be partly mediated through the STAT3 pathway.

关 键 词：CELECOXIB nasopharyngeal carcinoma APOPTOSIS cell cycle STAT3 

分 类 号：Q2[生物学—细胞生物学] Q756