阿法替尼联合西妥昔单抗治疗非小细胞肺癌EGFR T790M突变所致的吉非替尼耐药  

Overcoming acquired resistance to gefitinib in NSCLC with EGFR T790M mutation using combination of afatinib and cetuximab

作　　者：李静[1] 武新虎[1] 刘志冰[1] 王振[1] 宋勇[2] 朱锡旭[1] 

机构地区：[1]南京军区南京总医院放疗科,江苏南京210002 [2]南京军区南京总医院呼吸内科,江苏南京210002

出　　处：《肿瘤》2013年第7期619-623,共5页Tumor

基　　金：2010年度南京军区医学科技创新基金(编号:10MA098)

摘　　要：目的:探讨阿法替尼联合西妥昔单抗对非小细胞肺癌(non-small cell lungcancer,NSCLC)表皮生长因子受体(epidermal growth factor receptor,EGFR)T790M突变所致继发性耐药的作用。方法:培养EGFRT790M突变所致继发性耐药的NSCLC患者的原代细胞,胶原凝胶体包埋药敏技术检测阿法替尼(10nmol/L)和西妥昔单抗(50μg/mL)对NSCLC原代细胞的敏感性,WST-1和FCM法观察联合用药对NSCLC原代细胞增殖和凋亡的影响。结果:阿法替尼联合西妥昔单抗对EGFRT790M突变阳性的继发性耐药的NSCLC原代细胞的敏感性高于单药组(P<0.05);阿法替尼联合西妥昔单抗组NSCLC原代细胞存活率低于单药组(P<0.05),而细胞凋亡率高于单药组(P<0.05)。结论:阿法替尼联合西妥昔单抗对EGFRT790M突变所致耐药的NSCLC原代细胞有效。Objective： To investigate the effect of afatinib combined with cetuximab on the acquired resistance in NSCLC （non-small cell lung cancer） with EGFR （epidermal growth factor receptor） T790M mutation. Methods： The sensitivity to afatinib （10 nmol/L） in combination with cetuximab （50 μg/mL） in the primary NSCLC cells with EGFR T790M mutation was investigated by CD-DST （collagen-gel droplet embedded-culture drug sensitivity test）. The proliferative and apoptotic rates of primary NSCLC cells after treatment with afatinib in combination with cetuximab were detected by cell proliferation assay （WST-1） and flow cytometry, respectively. Results： The sensitivity to combination of afatinib and cetuximab in the primary NSCLC cells with EGFR T790M mutation was higher than that to afatinib or cetuximab alone （P 〈 0.05）. The survival rate of the primary NSCLC cells after treatment with afatinib and cetuximab was lower than that in the cells treated with afatinib or cetuximab alone （P 〈 0.05）, whereas the apoptotic rate was reverse （P 〈 0.05）. Conclusion： Afatinib in combination with cetuximab is effective to reverse resistance to gefitinib in primary NSCLC cells with EGFR T790M mutation.

关 键 词：癌 非小细胞肺 受体 表皮生长因子 细胞凋亡 阿法替尼 西妥昔单抗 

分 类 号：R734.2[医药卫生—肿瘤]