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.