Epithelial-to-mesenchymal transition correlates with gefitinib resistance in NSCLC cells and the liver X receptor ligand GW3965 reverses gefitinib resistance through inhibition of vimentin

OncoTargets and Therapy
Yong HuJi-Feng Feng

Abstract

The role of epithelial-to-mesenchymal transition in cancer drug resistance is increasingly acknowledged. We examined whether epithelial-to-mesenchymal transition affects gefitinib resistance in non-small cell lung cancer (NSCLC) cells. Cell viability was detected by CCK-8 assay, VIM expression levels were determined by quantitative real-time polymerase chain reaction. Western blot and immunocytochemistry were performed to determine the protein expression level of vimentin. We observed morphologic differences between gefitinib-sensitive and -insensitive cells. Compared with the sensitive parental cell line, HCC827, vimentin expression levels were increased in HCC827 cells with acquired gefitinib resistance. Vimentin expression was also markedly upregulated in cells with intrinsic gefitinib resistance, and upregulated vimentin expression was correlated with gefitinib sensitivity. Our previous study demonstrated that coadministration of gefitinib and GW3965 resulted in decreased cell proliferation and induced apoptosis. Therefore, we investigated the relationship among GW3965, vimentin, and gefitinib resistance in NSCLC cells by analysis of the expression of vimentin in cells treated with a combination of gefitinib and GW3965. Gef...Continue Reading

Citations

Jul 17, 2020·British Journal of Pharmacology·Lorenzo Pontini, Maura Marinozzi
Aug 14, 2020·Cancers·Alessandra CaligiuriAlessandra Gentilini
Mar 14, 2018·Breast Cancer Research and Treatment·Tia H TurnerJ Chuck Harrell
Dec 10, 2019·Journal of Hematology & Oncology·Zuan-Fu Lim, Patrick C Ma
Dec 18, 2019·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Joanna KopeckaChiara Riganti
Dec 29, 2020·Frontiers in Pharmacology·Yi ShiJianzhong Shen
May 20, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Liyun LiuHou-Wen Lin

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Methods Mentioned

BETA
enzyme-linked immunosorbent assay
PCR
electrophoresis

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Apoptosis

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