摘要
目的:探讨培美曲塞联合吉非替尼对体外诱导的表皮生长因子受体-酪氨酸激酶抑制剂(epidermal growth factor receptor-tyrosine kinase inhibitor,EGFR-TKI)获得性耐药的人非小细胞肺癌PC9/吉非替尼耐药(gei tinib resistance,GR)细胞株的效应及其可能的机制。方法:吉非替尼和培美曲塞单药或联合作用于PC9/GR细胞后,MTT法检测各药物处理组细胞的增殖抑制率及药物的联合指数(combination index,CI),FCM法检测各组细胞的凋亡率,蛋白质印迹法检测各组细胞磷酸化AKT和Bcl-2蛋白的表达水平。结果:吉非替尼和培美曲塞联合应用对PC9/GR细胞的增殖抑制作用和促凋亡作用明显强于各单药组(P<0.05);吉非替尼和培美曲塞的CI值<1,表现出明显的协同效应。与未进行药物处理的对照组比较,培美曲塞联合吉非替尼可明显下调PC9/GR细胞中磷酸化AKT和Bcl-2蛋白的表达水平(P<0.01)。结论:培美曲塞联合吉非替尼对PC9/GR细胞具有较好的协同作用,这协同作用可能与诱导细胞凋亡和下调磷酸化AKT蛋白表达有关。
Objective： To investigate the efficacy of pemetrexed in combination with gefitinib on human non-small cell lung cancer PC9/gefitinib resistance （GR） cells with acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitor （EGFR-TKI）, and to explore the possible mechanism. Methods： PC9/GR cells were exposured to either gefitinib or pemetrexed alone or combination. The proliferative inhibition rates and the combination index （CI） values of PC9/GR cells in different treatment groups were detected by MTT assay. The apoptotic rates of PC9/GR cells in different treatment groups were detected by flow cytometry. The expression levels of phospho-AKT （p-AKT） and Bcl-2 of PC9/GR cells in different treatment groups were analyzed by Western blotting. Results： The proliferative inhibition rate and the apoptotic rate of PC9/GR cells in combination of gefltinib and pemetrexed group were higher than those in gefltinib or pemetrexed alone group （P 〈 0.05）. The CI value of gefitinib plus pemetrexed was less than each alone, which had a synergistic effect. As compared with the control （PC9/GR cells without any treatment）, the expression levels of p-AKT and Bcl-2 proteins of PC9/GR cells in combination of gefitinib and pemetrexed group were decreased （P 〈 0.01 ）. Conclusion： The combination of pemetrexed and gefitinib generats a synergistic effect in PC9/GR cells. This effect may be related to apoptosis and down-regulation the expression of p-AKT.
出处
《肿瘤》
CAS
CSCD
北大核心
2014年第2期128-134,共7页
Tumor
关键词
癌
非小细胞肺
药物疗法
联合
细胞增殖
吉非替尼
培美曲塞
Carcinoma, non-small cell lung
Drug therapy, combination
Cell proliferation
Gefitinib
Pemetrexed
