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Nimotuzumab enhances the sensitivity of non-small cell lung cancer cells to tumor necrosis factor-α by inhibiting the nuclear factor-кB signaling pathway

  • Authors:
    • Jing Zhu
    • Ying Xin
    • Xiaoliang Liu
    • Ying Wang
    • Ying Liu
  • View Affiliations / Copyright

    Affiliations: Department of Thoracic Oncology, Cancer Hospital of Jilin Province, Changchun, Jilin 130012, P.R. China, Department of Blood Cancer, The First Affiliated Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
    Copyright: © Zhu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 3345-3351
    |
    Published online on: February 12, 2018
       https://doi.org/10.3892/etm.2018.5856
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Abstract

Non-small cell lung cancer (NSCLC) accounts for ~85% of lung cancer cases worldwide. Current guidelines recommend the use of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors for patients with NSCLC. The EGF/EGFR signaling pathway has been demonstrated to activate nuclear factor (NF)‑κB, which may inhibit tumor necrosis factor (TNF)-α induced cell apoptosis. The aim of the present study was to investigate whether inhibiting the EGF/EGFR signaling pathway sensitizes NSCLC cell lines to TNF‑α‑induced apoptosis. The resistance of NSCLC cell lines to TNF‑α was evaluated by cell viability assay. The effect of nimotuzumab (Ni) on NSCLC cell sensitivity to TNF‑α, as well as the role of NF‑κB in mediating resistance to TNF‑α‑induced apoptosis, was explored by western blot analysis, cell viability assay, apoptosis assay and an NF‑κB DNA binding assay. It was demonstrated that EGFR protein expression was markedly higher in the H292 and H1975 cell lines compared with H460 and H1299 cell lines. H292 and H1975 also exhibited significantly increased TNF‑α resistance compared with H460 and H1299 cells. Low dose Ni treatment slightly reduced the viability of H292 and H1975 cells; however, combined treatment with low dose Ni and TNF‑α significantly inhibited H292 and H1299 cell viability compared with H460 and H1299 cells by inducing cell apoptosis. NF‑κB protein expression and activity were also inhibited by the combination treatment. TNF‑α treatment alone induced apoptosis in NF‑κB deficient H292 and H1975 cells, similar to the effect of combination treatment in wild type H292 and H1975 cells. The results of the present study suggest that Ni sensitizes NSCLC cell lines to TNF‑α‑induced cell death by inhibiting NF‑κB protein expression and activation, indicating a novel mechanism by which Ni suppresses the development of NSCLC.
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Copy and paste a formatted citation
Spandidos Publications style
Zhu J, Xin Y, Liu X, Wang Y and Liu Y: Nimotuzumab enhances the sensitivity of non-small cell lung cancer cells to tumor necrosis factor-α by inhibiting the nuclear factor-кB signaling pathway. Exp Ther Med 15: 3345-3351, 2018.
APA
Zhu, J., Xin, Y., Liu, X., Wang, Y., & Liu, Y. (2018). Nimotuzumab enhances the sensitivity of non-small cell lung cancer cells to tumor necrosis factor-α by inhibiting the nuclear factor-кB signaling pathway. Experimental and Therapeutic Medicine, 15, 3345-3351. https://doi.org/10.3892/etm.2018.5856
MLA
Zhu, J., Xin, Y., Liu, X., Wang, Y., Liu, Y."Nimotuzumab enhances the sensitivity of non-small cell lung cancer cells to tumor necrosis factor-α by inhibiting the nuclear factor-кB signaling pathway". Experimental and Therapeutic Medicine 15.4 (2018): 3345-3351.
Chicago
Zhu, J., Xin, Y., Liu, X., Wang, Y., Liu, Y."Nimotuzumab enhances the sensitivity of non-small cell lung cancer cells to tumor necrosis factor-α by inhibiting the nuclear factor-кB signaling pathway". Experimental and Therapeutic Medicine 15, no. 4 (2018): 3345-3351. https://doi.org/10.3892/etm.2018.5856
Copy and paste a formatted citation
x
Spandidos Publications style
Zhu J, Xin Y, Liu X, Wang Y and Liu Y: Nimotuzumab enhances the sensitivity of non-small cell lung cancer cells to tumor necrosis factor-α by inhibiting the nuclear factor-кB signaling pathway. Exp Ther Med 15: 3345-3351, 2018.
APA
Zhu, J., Xin, Y., Liu, X., Wang, Y., & Liu, Y. (2018). Nimotuzumab enhances the sensitivity of non-small cell lung cancer cells to tumor necrosis factor-α by inhibiting the nuclear factor-кB signaling pathway. Experimental and Therapeutic Medicine, 15, 3345-3351. https://doi.org/10.3892/etm.2018.5856
MLA
Zhu, J., Xin, Y., Liu, X., Wang, Y., Liu, Y."Nimotuzumab enhances the sensitivity of non-small cell lung cancer cells to tumor necrosis factor-α by inhibiting the nuclear factor-кB signaling pathway". Experimental and Therapeutic Medicine 15.4 (2018): 3345-3351.
Chicago
Zhu, J., Xin, Y., Liu, X., Wang, Y., Liu, Y."Nimotuzumab enhances the sensitivity of non-small cell lung cancer cells to tumor necrosis factor-α by inhibiting the nuclear factor-кB signaling pathway". Experimental and Therapeutic Medicine 15, no. 4 (2018): 3345-3351. https://doi.org/10.3892/etm.2018.5856
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