Ionizing Radiation Reduces TKI Resistance Caused by T790M Mutation in NSCLC Cell Lines
10.3779/j.issn.1009-3419.2015.08.02
- VernacularTitle:电离辐射降低NSCLC细胞株T790M突变所致TKI耐药
- Author:
LI JING
1
;
WU XINHU
;
WANG ZHEN
;
SHEN ZETIAN
;
SUN NI
;
ZHU XIXU
Author Information
1. 南京大学医学临床学院南京军区南京总医院
- Keywords:
Lung neoplasms;
Radiosensitivity;
EGFR-TKI;
Drug tolerance;
T790M mutation;
L858R mutation
- From:
Chinese Journal of Lung Cancer
2015;(8):475-480
- CountryChina
- Language:Chinese
-
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.
