中国肺癌杂志Issue(8)：475-480,6.DOI:10.3779/j.issn.1009-3419.2015.08.02
电离辐射降低NSCLC细胞株T790M突变所致TKI耐药
Ionizing Radiation Reduces TKI Resistance Caused by T790M Mutation in NSCLC Cell Lines
摘要
Abstract
Background and objectiveEpidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), which targets EGFR, plays an important role in non-small cell lung cancer (NSCLC) treatment. Patients with somatic acti-vating mutations in theEGFR gene exhibit signiifcant initial response but eventually develop resistance to TKI. hTe second mutation (T790M) of theEGFR gene is the possible main cause of drug resistance. hTe aim of this study is to investigate the effect of ionizing radiation on EGFR-TKI resistance caused by T790M mutation in NSCLC cell lines.MethodsWe selected H1975 and H3255 as research subjects and tested the mutation states by real-time PCR analysis. Radiosensitivity was deter-mined by clone-forming test, and drug resistance was detected in different groups by MTT assay.Results H1975 is anEGFR double mutant (L858R plus T790M), whereas H3255 is anEGFR single mutant (L858R). hTe cell survival fractions of H1975 and H3255 did not vary in different treatment groups (P=0.952). hTus, T790M mutation did not affect the radiosensitivity of NSCLC cell lines. hTe IC50 of H1975 in the 2.5 Gy group [(0.678; 2±0.373) μmol/L] was statistically signiifcant compared with that in the 0 Gy normal control group [(3.520±0.821) μmol/L] (P=0.008). hTe drug tolerance of the H1975 cell line by 89.5 dropped to 39.2 times.ConclusionIonizing radiation can reduce TKI resistance caused by T790M mutation in NSCLC cell lines. Our results provide a research basis for futurein vivo and clinical studies. Radiotherapy combined with EGFR-TKI treatment can be a promising strategy to overcome T790M-mediated drug resistance.关键词
肺肿瘤/放射敏感性/表皮生长因子受体酪氨酸激酶抑制剂/药物耐受性/T790M突变/L858R突变Key words
Lung neoplasms/Radiosensitivity/EGFR-TKI/Drug tolerance/T790M mutation/L858R mutation引用本文复制引用
李静,武新虎,王振,沈泽天,孙妮,朱锡旭..电离辐射降低NSCLC细胞株T790M突变所致TKI耐药[J].中国肺癌杂志,2015,(8):475-480,6.基金项目
本研究受南京军区南京总医院基金项目（No.2014049）资助hTis study was supported by the grant from Jinling Hospital (No.2014049) （No.2014049）
