联合靶向阻断EGFR和mTOR信号通路对鼻咽癌细胞生长影响的研究

Effect of cell growth inhibition through simultaneously targeted blocking epidermal growth factor receptor tyrosine kinase and mTOR signaling pathway in nasopharyngeal carcinoma

目的观察联合阻断表皮生长因子受体(EGFR)和雷帕霉素靶蛋白(mTOR)介导的信号通路对鼻咽癌细胞株CNE-1及CNE-2的影响。方法EGFR酪氨酸激酶拮抗剂(Tarceva)、mTOR抑制剂(Rapamycin)单独(单独处理组)和联合处理(联合处理组)鼻咽癌细胞株CNE-1及CNE-2后,CCK-8法检测细胞生长抑制率,流式细胞法检测细胞周期和凋亡率。结果①Tarceva、Rapamycin单独处理组对CNE-1和CNE-2细胞株均产生剂量依赖性抗增殖作用。②联合用药组CNE-1和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)。③联合处理组的G1期细胞比例大于单独处理组之和(P<0.05)。联合处理组的细胞凋亡率高于单独处理组(P<0.05)。结论Tarceva及Rapamycin联合靶向治疗能协同性地抑制鼻咽癌细胞生长,这种效应可能通过增加G1期细胞阻滞及凋亡来实现。

Objective The aim of the investigation was to verify that simultaneously blocking both EGFR and mTOR mediated pathways may be an efficient way to inhibit cell growth in nasopharyngeal carcinoma.Methods The effect of cell growth inhibition through a combination of EGFR-selective tyrosine kinase inhibitor Tarceva and mTOR inhibitor Rapamycin was evaluated.Cell growth assay and flow cytometric analysis were applied to assessing the cell cycle and apoptosis in both CNE-1 and CNE-2 cell lines.Results ① Tarceva and Rapamycin demonstrated a concentration dependent anti-proliferative effect on both CNE-1 and CNE-2 cell lines（P0.05）.② The inhibition rate of cell growth in the group treated with a combination of two agents was higher than the sum of that in the two groups treated with only one agent（P0.05）.③ The combination of Tarceva and Rapamycin significantly induced G1 cell arrest（P0.05）and increased apoptosis rate（P0.05）compared with the groups treated with single agent and the control group.Conclusion Results of the investigation suggest that a combination of Tarceva and Rapamycin induced cell growth inhibition in a synergistic way,which may be resulted from the increased rates of G1 cell arrest and apoptosis.