title: Inhibition of elongation factor-2 kinase augments the antitumor activity of Temozolomide against glioma.
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.
  
  
  RESULTS
  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
  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.
authors.affiliation: Department of Pharmacology, College of Pharmaceutical Sciences, Cyrus Tang Hematology Center, Affiliated Changshu Hospital, Soochow University, Suzhou, Jiangsu, China.
authors.forename: Xiao-Yuan
authors.initials: XY
authors.lastname: Liu
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Jianping
authors.initials: J
authors.lastname: Wu
authors.forename: Lei
authors.initials: L
authors.lastname: Zhou
authors.forename: Yi-Jie
authors.initials: YJ
authors.lastname: Ren
authors.forename: Wei-Qiong
authors.initials: WQ
authors.lastname: Yang
authors.forename: Zi-Jun
authors.initials: ZJ
authors.lastname: Ming
authors.forename: Bo
authors.initials: B
authors.lastname: Chen
authors.forename: Jianrong
authors.initials: J
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jin-Ming
authors.initials: JM
authors.lastname: Yang
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D004195:Disease Models, Animal; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004357:Drug Synergism; D054736:Elongation Factor 2 Kinase / Q000037:antagonists & inhibitors / Q000235:genetics*; D005910:Glioma / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D034622:RNA Interference; D000077204:Temozolomide; D023041:Xenograft Model Antitumor Assays
chemical_list: D018906:Antineoplastic Agents, Alkylating; D047428:Protein Kinase Inhibitors; D003606:Dacarbazine; D054736:Elongation Factor 2 Kinase; D000077204:Temozolomide