Inhibition of elongation factor-2 kinase augments the antitumor activity of temozolomide against glioma

Xiao Yuan Liu, Li Zhang, Jian Ping Wu, Lei Zhou, Yi Jie Ren, Wei Qiong Yang, Zi Jun Ming, Bo Chen, Jianrong Wang, Yi Zhang, Jin Ming Yang

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Background: Glioblastoma multiforme (GBM), the most common form of brain cancer with an average survival of less than 12 months, is a highly aggressive and fatal disease characterized by survival of glioma cells following initial treatment, invasion through the brain parenchyma and destruction of normal brain tissues, and ultimately resistance to current treatments. Temozolomide (TMZ) is commonly used chemotherapy for treatment of primary and recurrent high-grade gliomas. Nevertheless, the therapeutic outcome of TMZ is often unsatisfactory. In this study, we sought to determine whether eEF-2 kinase affected the sensitivity of glioma cells to treatment with TMZ. Methodology/Principal Findings: Using RNA interference approach, a small molecule inhibitor of eEF-2 kinase, and in vitro and in vivo glioma models, we observed that inhibition of eEF-2 kinase could enhance sensitivity of glioma cells to TMZ, and that this sensitizing effect was associated with blockade of autophagy and augmentation of apoptosis caused by TMZ. Conclusions/Significance: These findings demonstrated that targeting eEF-2 kinase can enhance the anti-glioma activity of TMZ, and inhibitors of this kinase may be exploited as chemo-sensitizers for TMZ in treatment of malignant glioma.

Original languageEnglish (US)
Article numbere81345
JournalPloS one
Volume8
Issue number11
DOIs
StatePublished - Nov 26 2013

All Science Journal Classification (ASJC) codes

  • General

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