盐酸埃克替尼与多西他赛、培美曲塞不同联合方式对非小细胞肺癌PC-9细胞系作用的实验研究  

Synergistic Interaction of Icotinib with Pemetrexed or Docetaxel in Different Combinations on Inducing the Apoptosis of PC-9 Cell

作　　者：郭磊[1] 王键玮 李爱洁[1] 汪进良[1] 刘欢[2] 李春晓[2] 王海娟[2] 钱海利[2] 胡毅[1] 

机构地区：[1]解放军总医院肿瘤内一科,北京100853 [2]中国医学科学院肿瘤医院分子肿瘤学国家重点实验室,北京100021

出　　处：《现代生物医学进展》2015年第22期4257-4262,共6页Progress in Modern Biomedicine

基　　金：中国老年学学会课题(CGOS-03-2014-1-1-00500)

摘　　要：目的:探讨盐酸埃克替尼以不同次序联合多西他赛、培美曲塞对非小细胞肺癌细胞系PC-9的作用。方法:运用xCELLigence系统检验多西他赛、培美曲塞、盐酸埃克替尼单药作用于PC-9细胞系的半数抑制浓度(Half maximal inhibitory concentration,IC50),用流式细胞仪检测埃克替尼与多西他赛/培美曲塞联合的不同组合方式对PC-9细胞系的细胞周期影响及凋亡。结果:1埃克替尼对PC-9细胞作用60 h后的IC50值为5.3μM;多西他赛对PC-9细胞作用36 h后的IC50为21.5 mg·m L-1;培美曲塞对PC-9细胞作用36 h后的IC50为30μM。2Annexin V-FITC凋亡实验观察到化疗药先于埃克替尼应用对靶细胞的体外杀伤作用均明显高于其他各组,先用多西他赛组细胞凋亡率为(23±0.2)%,高于先用埃克替尼组(10.2±0.1)%和两药同时用药组(15.8±0.4)%;先用培美曲塞组细胞凋亡率为(36.3±0.03)%,高于先用埃克替尼组(14.7±0.1)%和两药同时用药组(30.6±0.03)%,差异有统计学意义(P<0.05)。3流式细胞仪周期检测结果显示埃克替尼先于多西他赛(或培美曲塞)用药或两药同时应用时PC-9细胞G0/G1期比例比多西他赛(或培美曲塞)先于埃克替尼用药组高。结论:多西他赛、培美曲塞先于埃克替尼应用方案对肿瘤细胞杀伤作用优于晚用埃克替尼或同时应用埃克替尼。Objective： To investigate the effects of icotnib combined with chemothempy drugs （docetaxel,pemetrexed）on lung carcinoma cell line PC-9. Methods： The half maximal inhibitory concentration of docetaxel, pemetrexed and icotinib were analyzed by xCELLigence. Flow cytometry was used to detect cell cycle and apoptosis rate of PC-9 cell after different treatment. Results： （1）The IC50 of icotinib after dosing for 60 hours was 5.3 μM; The IC50 of doeetaxel after dosing for 36 hours was 21.5 mg -mL-1; the IC50 of pemetrexed after dosing for 36 hours was 30 μM. （2）AnnexinV-FITC apoptosis experiment showed that the apoptosis rate of sequential administration that docetaxel or pemetrexed followed by icotinib was significantly higher than other groups（P〈0.05）： the apoptosis rate of sequential administration that docetaxel followed by icotinib was （23± 0.2）%, which was higher than the sequential administration that icotinib followed by docetaxel and the administration that icotinib the same time with docetaxel; the apoptosis rate of sequential administration that pemetrexed followed by icotinib was（36.3± 0.03）%, which was higher than the sequential administration that icotinib followed by pemetrexed and the administration that icotinib the same time with pemetrexed.（3）The flow cytometry showed that the G0/G1 cell cycle of PC-9 processed by the sequential administration of docetaxel （pemetrexed） followed by icotinib was higher than the other administrations. Conclusion： Sequential administration of docetaxel or pemetrexed followed by icotinib is optimal combination schedule for the antiproliferative effects of NSCLC cells than other sequential administrations.

关 键 词：埃克替尼 多西他赛 培美曲塞 肺癌 

分 类 号：R734.2[医药卫生—肿瘤]