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

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.

journal_name

Oncol Lett

journal_title

Oncology letters

authors

Huang H,Song J,Liu Z,Pan L,Xu G

doi

10.3892/ol.2017.7446

subject

Has Abstract

pub_date

2018-02-01 00:00:00

pages

1487-1494

issue

2

eissn

1792-1074

issn

1792-1082

pii

OL-0-0-7446

journal_volume

15

pub_type

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