Axl is a novel target of celastrol that inhibits cell proliferation and migration, and increases the cytotoxicity of gefitinib in EGFR mutant non‑small cell lung cancer cells

  • Authors:
    • Youn Ju Lee
    • So‑Young Kim
    • Chuhee Lee
  • View Affiliations

  • Published online on: February 14, 2019     https://doi.org/10.3892/mmr.2019.9957
  • Pages: 3230-3236
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Abstract

Gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR‑TKI) is an excellent therapeutic agent to treat EGFR mutation‑positive non‑small cell lung cancer (NSCLC). However, the initial response decreases as chemoresistance develops. In the present study, gefitinib‑resistant EGFR mutant NSCLC PC‑9/GR cells were established to examine the characteristics and mechanisms associated with chemoresistance. Axl expression in PC‑9/GR cells was transcriptionally upregulated, since Axl protein and mRNA expression levels were identified to be increased according to western blot analysis and reverse transcription polymerase chain reaction results. The inhibitory effect of celastrol on Axl protein expression level, cell viability and clonogenicity were identified in parental and gefitinib‑resistant PC‑9 cells. In addition, treatment of PC‑9/GR cells with celastrol and gefitinib in combination was demonstrated to synergistically suppress Axl protein expression level, cell proliferation and migration. Taken together, upregulation of Axl expression seems to be associated with chemoresistance of PC‑9/GR cells. Furthermore, celastrol targets Axl to exert its anticancer effects in order to increase the susceptibility of PC‑9/GR cells to gefitinib and overcome chemoresistance.
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April-2019
Volume 19 Issue 4

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Lee YJ, Kim SY and Lee C: Axl is a novel target of celastrol that inhibits cell proliferation and migration, and increases the cytotoxicity of gefitinib in EGFR mutant non‑small cell lung cancer cells. Mol Med Rep 19: 3230-3236, 2019
APA
Lee, Y.J., Kim, S., & Lee, C. (2019). Axl is a novel target of celastrol that inhibits cell proliferation and migration, and increases the cytotoxicity of gefitinib in EGFR mutant non‑small cell lung cancer cells. Molecular Medicine Reports, 19, 3230-3236. https://doi.org/10.3892/mmr.2019.9957
MLA
Lee, Y. J., Kim, S., Lee, C."Axl is a novel target of celastrol that inhibits cell proliferation and migration, and increases the cytotoxicity of gefitinib in EGFR mutant non‑small cell lung cancer cells". Molecular Medicine Reports 19.4 (2019): 3230-3236.
Chicago
Lee, Y. J., Kim, S., Lee, C."Axl is a novel target of celastrol that inhibits cell proliferation and migration, and increases the cytotoxicity of gefitinib in EGFR mutant non‑small cell lung cancer cells". Molecular Medicine Reports 19, no. 4 (2019): 3230-3236. https://doi.org/10.3892/mmr.2019.9957