Synergistic interaction between MEK inhibitor and gefitinib in EGFR‑TKI‑resistant human lung cancer cells

  • Authors:
    • Suxia Li
    • Suxiu Chen
    • Yiyan Jiang
    • Jiefan Liu
    • Xiaolei Yang
    • Shichao Quan
  • View Affiliations

  • Published online on: August 6, 2015     https://doi.org/10.3892/ol.2015.3577
  • Pages: 2652-2656
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Abstract

With the increasing use of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR‑TKIs) in patients with advanced non‑small cell lung cancer (NSCLC), acquired resistance has become a major clinical problem. A combination of different signaling pathway inhibitors is a promising strategy to overcome this. In the present study, the mitogen‑activated protein kinase kinase 1/2 inhibitor, AZD6244, was used in combination with gefitinib to investigate the efficacy of this treatment in NSCLC cell lines, particularly in gefitinib‑resistant cells. The EGFR‑TKI‑sensitive PC‑9 (mutant EGFR/wild‑type K‑Ras) and EGFR‑TKI‑resistant A549 (wild‑type EGFR/mutant K‑Ras) human NSCLC cell lines were treated with AZD6244 alone, gefitinib alone or the combination of the two drugs, and the effects were evaluated using cell proliferation assays, with alterations in signaling pathways analyzed by western blotting. It was found that the growth inhibitory effect of combination treatment with gefitinib and AZD6244 was greater than that of gefitinib alone in the EGFR‑TKI‑resistant A549 cells. Treatment of A549 cells with gefitinib alone reduced the expression level of the activated form of Akt, and the combination of the two drugs showed stronger inhibition of phosphorylated‑Akt and phosphorylated‑extracellular signal‑regulated kinases. The data showed that the combination of AZD6244 and gefitinib exhibited dose‑dependent synergism in gefitinib‑resistant NSCLC cells. Thus, a preclinical rationale exists for the use of AZD6244 to enhance the efficacy of gefitinib in patients with EGFR‑TKI‑resistant NSCLC.
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October-2015
Volume 10 Issue 4

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Li S, Chen S, Jiang Y, Liu J, Yang X and Quan S: Synergistic interaction between MEK inhibitor and gefitinib in EGFR‑TKI‑resistant human lung cancer cells. Oncol Lett 10: 2652-2656, 2015.
APA
Li, S., Chen, S., Jiang, Y., Liu, J., Yang, X., & Quan, S. (2015). Synergistic interaction between MEK inhibitor and gefitinib in EGFR‑TKI‑resistant human lung cancer cells. Oncology Letters, 10, 2652-2656. https://doi.org/10.3892/ol.2015.3577
MLA
Li, S., Chen, S., Jiang, Y., Liu, J., Yang, X., Quan, S."Synergistic interaction between MEK inhibitor and gefitinib in EGFR‑TKI‑resistant human lung cancer cells". Oncology Letters 10.4 (2015): 2652-2656.
Chicago
Li, S., Chen, S., Jiang, Y., Liu, J., Yang, X., Quan, S."Synergistic interaction between MEK inhibitor and gefitinib in EGFR‑TKI‑resistant human lung cancer cells". Oncology Letters 10, no. 4 (2015): 2652-2656. https://doi.org/10.3892/ol.2015.3577