title: Inhibition of heat shock protein response enhances PS-341-mediated glioma cell death.
abstract: BACKGROUND
  Previous study indicated that PS-341 induces cell death via JNK pathway in vitro in glioma. However, suppressing proteasome complex by PS-341 may induce expression of heat shock proteins (HSPs), which confer potential protection against cellular stress. In this study, we explored whether induction of HSPs could impair PS-341-induced cell death and whether inhibition of HSPs could enhance cell damage induced by PS-341 in glioma cells.
  
  
  METHODS
  HSP expression in glioma cells was modulated by HSP inhibitor, sublethal heat, or knockdown of heat shock factor1 (HSF1), then PS-341-induced cell damage was examined by different methods. Similar experiments were also performed in HSF1+/+ and HSF1-/- cells. HSP70 expression and HSF1 nuclear localization were compared between glioma and normal brain tissues.
  
  
  RESULTS
  HSP level was upregulated mediated by HSF1 when glioma cells were treated with PS-341. PS-341-mediated cell damage could be significantly augmented by HSP inhibition. Furthermore, HSP70 expression and HSF1 nuclear localization were much more abundant in gliomas than in normal brain tissues.
  
  
  CONCLUSIONS
  Our results demonstrated that HSP70 impaired cell death induced by PS-341 in glioma cells. Administration of PS-341 in combination with either HSP70 inhibitor or HSF1 knockdown may act as a new approach to treatment of glioma.
authors: Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, The People's Republic of China.
authors: Yaohua
authors: Y
authors: Liu
authors: Tianhu
authors: T
authors: Zheng
authors: Shiguang
authors: S
authors: Zhao
authors: Huailei
authors: H
authors: Liu
authors: Dayong
authors: D
authors: Han
authors: Yunbo
authors: Y
authors: Zhen
authors: Dongxiao
authors: D
authors: Xu
authors: Yu
authors: Y
authors: Wang
authors: Hongyu
authors: H
authors: Yang
authors: Guang
authors: G
authors: Zhang
authors: Chunlei
authors: C
authors: Wang
authors: Jianing
authors: J
authors: Wu
authors: Yuanzhu
authors: Y
authors: Ye
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001559:Benzhydryl Compounds / Q000494:pharmacology; D001897:Boronic Acids / Q000494:pharmacology*; D000069286:Bortezomib; D001921:Brain / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D005909:Glioblastoma / Q000378:metabolism*; D050956:HSP40 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D000076249:Heat Shock Transcription Factors; D006358:Hot Temperature; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011719:Pyrazines / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000494:pharmacology; D034741:RNA, Small Interfering; D014157:Transcription Factors / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D001559:Benzhydryl Compounds; D001897:Boronic Acids; D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; C410027:KNK 437; D011719:Pyrazines; D011760:Pyrrolidinones; D034741:RNA, Small Interfering; D014157:Transcription Factors; D000069286:Bortezomib; D048031:JNK Mitogen-Activated Protein Kinases