Autophagy inhibition facilitates erlotinib cytotoxicity in lung cancer cells through modulation of endoplasmic reticulum stress

  • Authors:
    • Zhongliang Wang
    • Tingting Du
    • Xiaorong Dong
    • Zhenyu Li
    • Gang Wu
    • Ruiguang Zhang
  • View Affiliations

  • Published online on: April 1, 2016     https://doi.org/10.3892/ijo.2016.3468
  • Pages: 2558-2566
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Abstract

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have revolutionized the treatment for non-small cell lung cancer patients, but acquired resistance limit the efficiency of this treatment. As a homeostatic cellular recycling mechanism, autophagy has been proposed to participate in the EGFR-TKI resistance. However, the role of autophagy in lung cancer treatment and the underlying mechanisms have not been clarified. In this study, we found the sensitivity to erlotinib, a well-used EGFR-TKI, was correlated with basal autophagy level. Erlotinib was able to induce autophagy not only in TKI-sensitive, but also TKI-resistant cancer cells. Inhibition of autophagy significantly enhanced cytotoxicity of erlotinib in TKI-resistant cancer cells via modulation of endoplasmic reticulum (ER) stress induced apoptosis. In this process, CCAAT/enhancer binding protein homologous protein (CHOP) acted as an executioner. Downregulation of CHOP with siRNA blocked the autophagy inhibition and erlotinib co-treatment induced apoptosis and prevented cancer cells from this co-treatment-induced cell death. Our findings suggest that autophagy inhibition overcomes erlotinib resistance through modulation of ER stress mediated apoptosis.
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June-2016
Volume 48 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Wang Z, Du T, Dong X, Li Z, Wu G and Zhang R: Autophagy inhibition facilitates erlotinib cytotoxicity in lung cancer cells through modulation of endoplasmic reticulum stress. Int J Oncol 48: 2558-2566, 2016
APA
Wang, Z., Du, T., Dong, X., Li, Z., Wu, G., & Zhang, R. (2016). Autophagy inhibition facilitates erlotinib cytotoxicity in lung cancer cells through modulation of endoplasmic reticulum stress. International Journal of Oncology, 48, 2558-2566. https://doi.org/10.3892/ijo.2016.3468
MLA
Wang, Z., Du, T., Dong, X., Li, Z., Wu, G., Zhang, R."Autophagy inhibition facilitates erlotinib cytotoxicity in lung cancer cells through modulation of endoplasmic reticulum stress". International Journal of Oncology 48.6 (2016): 2558-2566.
Chicago
Wang, Z., Du, T., Dong, X., Li, Z., Wu, G., Zhang, R."Autophagy inhibition facilitates erlotinib cytotoxicity in lung cancer cells through modulation of endoplasmic reticulum stress". International Journal of Oncology 48, no. 6 (2016): 2558-2566. https://doi.org/10.3892/ijo.2016.3468