非小细胞肺癌EGFR基因少见突变P733L对第1代和第3代EGFR-TKI敏感性的研究  

Sensitivity of EGFR P733L Rare Mutation to the First-and Third-Generation EGFR-TKIs in Non-Small Cell Lung Cancer

作　　者：车娟娟[1] 王婧[1] 甄洪超[1] 林海珊[1] 尚昆[1] 俞静[1] CHE Juanjuan;WANG Jing;ZHEN Hongchao;LIN Haishan;SHANG Kun;YU Jing(Dept.of Oncology,Beijing Friendship Hospital,Capital Medical University,Beijing 100050,China)

机构地区：[1]首都医科大学附属北京友谊医院肿瘤科,北京100050

出　　处：《中国医院用药评价与分析》2024年第7期774-777,782,共5页Evaluation and Analysis of Drug-use in Hospitals of China

基　　金：国家自然科学基金面上项目(No.81774221)。

摘　　要：目的:探讨表皮生长因子受体(EGFR)基因少见突变P733L对第1代和第3代EGFR酪氨酸激酶抑制剂(EGFR-TKI)的敏感性。方法:通过四唑盐比色法和平板克隆实验分析EGFR L858R和P733L肺癌细胞对第1代和第3代EGFR-TKI的敏感性;通过Transwell实验分析第1代和第3代EGFR-TKI对EGFR L858R和P733L肺癌细胞迁移的抑制作用;通过检测凋亡蛋白分析第1代和第3代EGFR-TKI促进EGFR L858R和P733L肺癌细胞凋亡的作用。结果:第1代和第3代EGFR-TKI对EGFR L858R和P733L细胞的增殖、克隆形成和细胞迁移都有抑制作用。与EGFR野生型肺癌细胞相比,第1代和第3代EGFR-TKI处理后,EGFR L858R和P733L细胞的EGFR激酶活性受到抑制,细胞凋亡明显增加。结论:EGFR P733L突变细胞对第1代和第3代EGFR-TKI的敏感性与EGFR L858R突变细胞的敏感性相似,本研究为EGFR基因少见突变从EGFR-TKI治疗中获益提供了实验证据。OBJECTIVE:To analyze the sensitivity of epidermal growth factor receptor(EGFR)P733L rare mutation to the first-and third-generation EGFR-tyrosine kinase inhibitor(TKIs)in non-small cell lung cancer.METHODS:Sensitivity of EGFR L858R and P733L to the first-and third-generation EGFR-TKIs was analyzed by MTT and clone formation experiments.Inhibition effect of the first-and third-generation EGFR-TKIs on the migration of EGFR L858R and P733L lung cancer cells was analyzed by Transwell assay.Role of the first-and third-generation EGFR-TKIs in promoting apoptosis of EGFR L858R and P733L lung cancer cells was analyzed by the detection of apoptosis proteins.RESULTS:The first-and third-generation EGFR-TKIs inhibited the cell proliferation,clone formation,and cell migration of EGFR L858R and P733L.Compared with the wild-type EGFR lung cancer cells,the EGFR kinase activity of EGFR L858R and P733L cells was inhibited and cell apoptosis increased significantly after the first-and third-generation EGFR-TKIs treatment.CONCLUSIONS:The sensitivity of EGFR P733L mutant cells to the first-and third-generation EGFR-TKIs is similar to that of EGFR L858R mutant cells,which provides experimental evidence for the benefit of rare mutations in EGFR gene from EGFR-TKIs treatment.

关 键 词：非小细胞肺癌 表皮生长因子受体酪氨酸激酶抑制剂 EGFR少见突变 EGFR P733L 药物敏感性 

分 类 号：R979.1[医药卫生—药品]