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EGFR TKIs联合化疗的给药顺序对NSCLC细胞促凋亡的影响

高峰 张泽峰 王涛 王瑞

中国现代医学杂志2018,Vol.28Issue(14):24-30,7.
中国现代医学杂志2018,Vol.28Issue(14):24-30,7.DOI:10.3969/j.issn.1005-8982.2018.014.005

EGFR TKIs联合化疗的给药顺序对NSCLC细胞促凋亡的影响

Effect of EGFR-TKIs and chemotherapy combinations and administration sequence on apoptosis of NSCLC cells

高峰 1张泽峰 1王涛 1王瑞1

作者信息

  • 1. 河北医科大学第四医院 胸外一科,河北 石家庄 050011
  • 折叠

摘要

Abstract

Objective To explore the effect of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and chemotherapeutic drug alone, concurrent and sequential administration on apoptosis of non-small cell lung cancer (NSCLC) cells with acquired TKI-resistance. Methods NSCLC cell lines with TKI-resistance gene mutations (T790M and cMET) such as PC9ER, H1975 and HCC827GR as well as TKI-sensitive gene mutation (exon 19) cell lines PC9 and HCC827 were selected. Cell viability was detected by MTS assay when chemotherapy drugs Cisplatin, Paclitaxel and TKI Erlotinib were used alone, in combination or in sequential administration for intervention of NSCLC cell lines, and verified using colony formation assay. The content of apoptosis marker cPARP in cell lysate was detected in each treatment group by Western blot. Results MTS assay and colony formation revealed that the combination of EGFR-TKIs and chemotherapeutic drugs could synergistically increase the cytotoxicity to NSCLC cell lines. Simultaneous use of EGFR-TKIs and chemotherapeutic drugs or chemotherapy followed by EGFR-TKIs provided the maximum intervention. Western blot showed that the apoptotic marker cPARP expression was significantly increased when two drugs were simultaneously used. Moreover, chemotherapy then EGFR-TKIs intervention could obtain a more powerful pro-apoptotic performance than the reverse order intervention. Conclusions The sequence of chemotherapy followed by EGFR-TKI is likely to be the most active strategy, and could have the greatest effect on apoptosis in cell lines with acquired TKI-resistance.

关键词

非小细胞肺癌/获得性耐药/化疗/表皮生长因子受体络氨酸激酶抑制剂

Key words

NSCLC/acquired resistance/chemotherapy/EGFR-TKIs

分类

医药卫生

引用本文复制引用

高峰,张泽峰,王涛,王瑞..EGFR TKIs联合化疗的给药顺序对NSCLC细胞促凋亡的影响[J].中国现代医学杂志,2018,28(14):24-30,7.

中国现代医学杂志

OACSTPCD

1005-8982

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