靶向联合阻断表皮生长因子受体和环氧化酶-2信号通路影响鼻咽癌细胞生长的研究

The effect of simultaneously blocking target epidermal growth factor receptor tyrosine kinase and cyclooxygenase-2 on the growth of NPC cell

目的:观察联合阻断表皮生长因子受体(EGFR)和环氧化酶-2(COX-2)介导的信号通路,对鼻咽癌细胞株CNE-2的影响。方法:用EGFR-酪氨酸激酶拮抗剂和COX-2抑制剂单独和联合处理鼻咽癌细胞株CNE-2,采用CCK-8法检测细胞生长抑制率,流式细胞术进行细胞周期、凋亡率的分析,Westernblot检测相关蛋白表达。结果:①联合用药组CNE-2细胞生长抑制率显著大于两者单独处理组生长抑制率之和(P<0.05);②联合处理组细胞G1期比例大于单独处理组(P<0.05)。联合处理组细胞凋亡率与单独处理组相比差异无统计学意义(P>0.05);③与单独处理组相比,联合处理组出现明显的p-EGFR,COX-2表达下调。结论:联合阻断EGFR和COX-2信号通路对抑制鼻咽癌细胞株CNE-2生长,增加G1期阻滞及抑制EGFR的磷酸化和COX-2的表达方面具有协同作用。

Objective：This study was designed to prove simultaneously blocking both EGFR and COX-2-mediated pathways may be an efficient means of inhibiting cancer cell growth in NPC. Method： A combination of tarceva （EGFR-selectivetyrosine kinase inhibitors） with celecoxib （Cox-2 inhibitor） was studied on its effects on cell growth, cell cycle progression, apoptosis and protein expression in CNE-2 cell lines by cell growth assay, flow cytometric analysis assay and Western blotting. Resuit：①The inhibition rate of cell growth was higher in the group treated with a combination of two agents than that the sum of rates of the two groups treated with only one agent （P〈0.05）. ②The combination of tarceva with celecoxib significantly induced G1 arrest（P〈0.05）, but did not increase apoptosis rate（P〉0. 05）. ③The group of combination showed less expressions of p-EGFR and COX-2 than any other group. Conclusion： Simultaneously blocking EGFR and COX-2 mediated pathways would significantly inhibit the growth of CNE-2 cell line, increase G1 arrest and reduce the expression levels of p-EGFR and COX-2.