首页|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

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

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

Non-small cell lung cancerEpidermal growth factor receptor-tyrosine kinase inhibitorEGFR rare mutationEGFR P733LDrug sensitivity

车娟娟、王婧、甄洪超、林海珊、尚昆、俞静

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首都医科大学附属北京友谊医院肿瘤科,北京 100050

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

国家自然科学基金面上项目

81774221

2024

中国医院用药评价与分析
中国医药生物技术协会,中国药房杂志社

中国医院用药评价与分析

CSTPCD
影响因子:1.142
ISSN:1672-2124
年,卷(期):2024.24(7)