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
车娟娟 1王婧 1甄洪超 1林海珊 1尚昆 1俞静1
作者信息
- 1. 首都医科大学附属北京友谊医院肿瘤科,北京 100050
- 折叠
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.
Abstract
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Key words
Non-small cell lung cancer/Epidermal growth factor receptor-tyrosine kinase inhibitor/EGFR rare mutation/EGFR P733L/Drug sensitivity引用本文复制引用
基金项目
国家自然科学基金面上项目(81774221)
出版年
2024
国家科技期刊平台
NSTL
万方数据