Gefitinib联合化疗药物用药次序对肺癌细胞系GLC-82的不同作用

Effects of gefitinib combined with chemotherapeutics on GLC-82

目的:探讨吉非替尼(gefitinib.,商品名IRESSA)以不同次序联合化疗药(奈达铂、多西他赛、酒石酸长春瑞滨)对EGFR免疫组化染色呈阴性的肺癌细胞系GLC-82的作用。方法:检验不同次序联合吉非替尼时化疗药奈达铂、多西他赛、酒石酸长春瑞滨的IC50,用流式细胞仪检测吉非替尼与化疗药联合的不同次序对GLC-82细胞的细胞周期、凋亡率、Bcl-2表达的影响,用Westernblot检测COX2蛋白的表达。结果:在化疗药之前或与化疗药同时使用吉非替尼将使化疗药的抑制率-药物浓度曲线不同程度右移,半数抑制浓度(IC50)升高,晚用吉非替尼比早用吉非替尼有较高的凋亡率、G0-G1期细胞比例,较低的S期细胞比例、较低的Bcl-2表达率和较低的COX2蛋白表达。结论:吉非替尼和化疗药联合需探寻最佳方案,晚于化疗药用吉非替尼效果优于早于化疗药用吉非替尼。

Objective： To investigate the effects of gefitinib combined with chemotherapy drugs （Nedaplatin, docetaxel,vinorelbine） on lung carcinoma cell line GLC-82. Methods： The IC50 of Nedaplatin,docetaxel,and vinorelbine combined with gefitinib in different sequence were analyzed. Cell cycle , apoptosis and Bcl-2 expression of GLC-82 cell were detected by flow cytometry,and COX2 protein was analyzed by western blot. Results： The inhibition ratio- concentration curve of chemotherapy drugs shifts right and IC50 was increased when gefitinib was used before or combined with chemotherapy drugs. Higher rate of apoptosis, GO-G1 cell proportion, lower rate of S cell proportion,and lower Bcl-2 and COX2 expressions were present when gefitinib was used after chemotherapy drugs. Conclusion： It is necessary to explore optimal schedule when gefitinib is combined with chemotherapy drugs. Gefitinib used after hemotherapy drugs creates better curative effects than before chemotherapy drugs.