Inhibition of endoplasmic reticulum stress-induced autophagy sensitizes melanoma cells to temozolomide treatment

  • Authors:
    • Oxana Ryabaya
    • Anastasia Prokofieva
    • Dmitry Khochenkov
    • Ivan Abramov
    • Alexander Zasedatelev
    • Evgenia Stepanova
  • View Affiliations

  • Published online on: May 9, 2018     https://doi.org/10.3892/or.2018.6430
  • Pages: 385-394
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Abstract

The incidence of malignant melanoma is increasing. The discovery of agents specifically targeting the mutated cascades has provided a good response for patients with oncogenic B-Raf proto-оncogene, serine/threonine kinase (BRAF). However, numerous studies continue to focus on novel methods of treatment to overcome acquired resistance to novel drugs. Recently, it has been revealed that inhibition of endoplasmic reticulum (ER) stress chaperon 78 kDa glucose-regulated protein 78 (GRP78) leads to down­regulation of autophagy and increased sensitivity to temozolomide (TMZ) treatment. Melanoma cells have a different sensitivity to TMZ treatment, which corresponds to the basal autophagy level. In the present study, we demonstrated that downregulation of GRP78 mitigated chemoresistance to TMZ in three melanoma cell lines. We found that downregulation of GRP78 led to inhibition of autophagy, cell cycle arrest in the G0/G1 phase, and activation of caspase-7-induced apoptosis, and this was affected by the initial autophagy level. Moreover, inhibition of GRP78 mitigated the combined TMZ and chloroquine effect. Our data revealed that autophagy inhibition through downregulation of ER stress response could overcome resistance to TMZ treatment in melanoma cells with a high basal level of autophagy treatment, which makes this combination a potential potent antitumor treatment for metastatic melanoma.
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July-2018
Volume 40 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Ryabaya O, Prokofieva A, Khochenkov D, Abramov I, Zasedatelev A and Stepanova E: Inhibition of endoplasmic reticulum stress-induced autophagy sensitizes melanoma cells to temozolomide treatment. Oncol Rep 40: 385-394, 2018.
APA
Ryabaya, O., Prokofieva, A., Khochenkov, D., Abramov, I., Zasedatelev, A., & Stepanova, E. (2018). Inhibition of endoplasmic reticulum stress-induced autophagy sensitizes melanoma cells to temozolomide treatment. Oncology Reports, 40, 385-394. https://doi.org/10.3892/or.2018.6430
MLA
Ryabaya, O., Prokofieva, A., Khochenkov, D., Abramov, I., Zasedatelev, A., Stepanova, E."Inhibition of endoplasmic reticulum stress-induced autophagy sensitizes melanoma cells to temozolomide treatment". Oncology Reports 40.1 (2018): 385-394.
Chicago
Ryabaya, O., Prokofieva, A., Khochenkov, D., Abramov, I., Zasedatelev, A., Stepanova, E."Inhibition of endoplasmic reticulum stress-induced autophagy sensitizes melanoma cells to temozolomide treatment". Oncology Reports 40, no. 1 (2018): 385-394. https://doi.org/10.3892/or.2018.6430