Cigarette smoke extract exposure induces EGFR-TKI resistance in EGFR-mutated NSCLC via mediating Src activation and EMT

Lung Cancer : Journal of the International Association for the Study of Lung Cancer
Dandan LiHong Chen

Abstract

The study aims to explore the molecular basis for the poor response of epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in EGFR mutated non-small cell lung cancer (NSCLC) patients with smoking history. Novel agent overcoming EGFR-TKI resistance had also been investigated. The impact of cigarette smoke extract (CSE) on gefitinib sensitive PC-9 cells was evaluated using quantitative real-time PCR (qRT-PCR), western blot, CCK-8 assays, immunofluorescence staining, matrigel invasion assays and wound healing assays. Western blot and qRT-PCR presented that CSE stimulated the up-regulation of Vimentin and down-regulation of E-cadherin in PC-9 cells in concentration-and time-dependent manners through modulating Src phosphorylation. N-acetylcysteine (NAC) was capable of decreasing Src phosphorylation, abrogating changes of epithelial to mesenchymal transition (EMT) markers instigated by CSE. Immunofluorescence staining found that PC-9 cells displayed features of mesenchymal cells after CSE exposure, while PP2 and NAC could recover these changes. CCK-8 assays showed that CSE could increase the IC50 of PC-9 cells, while PP2 and NAC could abort the elevation of IC50 caused by CSE. Matrigel invasion assays and wound ...Continue Reading

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Citations

Sep 20, 2016·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Kenichi SudaFred R Hirsch
Mar 20, 2018·Journal of Experimental & Clinical Cancer Research : CR·Meng-Shih WengMing-Hsien Chien
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Aug 5, 2017·Cancers·Antoine LegrasHélène Blons
Nov 5, 2019·Frontiers in Oncology·Xuan ZhuXing Niu
May 4, 2021·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Chen-Chen ZhangXiao-Long Fu
May 12, 2021·Biochimica Et Biophysica Acta. Reviews on Cancer·Jingshan CaiShengjun Wang

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