Open Access

Autophagy activation promotes bevacizumab resistance in glioblastoma by suppressing Akt/mTOR signaling pathway

  • Authors:
    • He Huang
    • Jian Song
    • Zheng Liu
    • Li Pan
    • Guozheng Xu
  • View Affiliations

  • Published online on: November 20, 2017     https://doi.org/10.3892/ol.2017.7446
  • Pages: 1487-1494
  • Copyright: © Huang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Glioblastomas are the most common primary and malignant brain tumors. The standard therapy includes surgery and radiotherapy plus chemotherapy, with additional bevacizumab to block the angiogenesis in tumors. However, the ever‑growing tolerance of glioblastomas to chemotherapeutic drugs impairs the clinical outputs of tumor treatment. The present study investigated the tolerance of glioblastomas to bevacizumab. Although bevacizumab resulted in direct anti‑proliferation and pro‑apoptosis effects on glioblastoma cells via downregulating the anti‑apoptotic proteins and upregulating the pro‑apoptotic proteins, tolerance was also encountered that was mainly caused by autophagy induction in tumor cells. The suppressed Akt‑mTOR signaling pathway led to the upregulated autophagy process. Blockade of the autophagy process significantly increased the tumor‑suppressive effect of bevacizumab on glioblastoma cells. To our knowledge, the present study is the first to report the involvement of autophagy in the tolerance of glioblastomas to bevacizumab. Therefore, autophagy inhibition may be considered a novel way to overcome the tolerance of glioblastomas to anti‑angiogenic agents.

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February 2018
Volume 15 Issue 2

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

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Copy and paste a formatted citation
APA
Huang, H., Song, J., Liu, Z., Pan, L., & Xu, G. (2018). Autophagy activation promotes bevacizumab resistance in glioblastoma by suppressing Akt/mTOR signaling pathway. Oncology Letters, 15, 1487-1494. https://doi.org/10.3892/ol.2017.7446
MLA
Huang, H., Song, J., Liu, Z., Pan, L., Xu, G."Autophagy activation promotes bevacizumab resistance in glioblastoma by suppressing Akt/mTOR signaling pathway". Oncology Letters 15.2 (2018): 1487-1494.
Chicago
Huang, H., Song, J., Liu, Z., Pan, L., Xu, G."Autophagy activation promotes bevacizumab resistance in glioblastoma by suppressing Akt/mTOR signaling pathway". Oncology Letters 15, no. 2 (2018): 1487-1494. https://doi.org/10.3892/ol.2017.7446