The Research Of Blocking EGFR And COX-2 Simultaneously To Treat NPC

Objective:Epidermal growth factor receptor(EGFR)and cyclooxygenase-2(Cox-2)contribute to development of nasopharyngeal carcinoma(NPC).We can use the EGFR inhibitors or Cox-2 inhibitors to cure the NPC.But the effect of single agent is not high.This study was designed to explore the effect of a combination of EGFR-selective tyrosine kinase inhibitors(TKIs)Tarceva with a Cox-2 inhibitor (Cox-2I)celecoxib on NPC cell lines CNE-1,CNE-2.Methods:The NPC cell lines CNE-1,CNE-2 was treated with the Tarceva and C elecoxib in a range of concentrations as single agents.Cell growth inhibition was measured by CCK-8.Then cells were treated with two drugs in fixed concentrations(Tarceva at 10 umol/L plus Celecoxib at 15 umol/L).Cell growth inhibition was measured by CCK-8.The cell cycle and apoptosis was measured by flow cytometric analysis.The exprssions of protein were also examined by using western blot after the combined treatment.Results:(1)The cell growth was inhibited by Tarceva and C elecoxib,and such effect showed a concentration-dependent manners in a certain range.The IC50 of C elecoxib is 25umol/l.The IC50 of Tarceva to CNE-1 is 35umol/l.The IC50 to CNE-2 is 15umol/l.(2)The combination of Tarceva with Celecoxib synergistically inhibited growth of CNE-2 cell lines(P＜0.05).(3)The combination of Tarceva with Celecoxib significantly induced G1 arrest(P＜0.05),but did not have higher apoptosis than the effect of single agent(P＞0.05).(4)the combination showed strong reductions of p-EGFR and COX-2Conclusions:(1)Blocking EGFR or COX-2 can inhibit growth of the CNE-2 cell lines,significantly induced G1 arrest and apoptosis.(2) Blocking EGFR and COX-2 Simultaneously can synergistically inhibited growth of CNE-2 cell lines,significantly induced G1 arrest.(3)Blocking EGFR and COX-2 Simultaneously synergistically reduce the level of p-EGFR and COX-2.