title: Inhibition of polo-like kinase 1 promotes hyperthermia sensitivity via inactivation of heat shock transcription factor 1 in human retinoblastoma cells.
abstract: OBJECTIVE
  Hyperthermia (HT) has been recognized as an effective focal treatment in retinoblastoma. However, one of the problems with HT therapy is that cells acquire acquisition. The purpose of this study was to evaluate whether the inhibition of polo-like kinase 1 (PLK1) would promote HT sensitivity in human retinoblastoma cells.
  
  
  METHODS
  We examined the effects of PLK1 knockdown by small interfering RNA (siRNA) or by the inhibition of PLK1 activity with PLK1 inhibitor (BI-2536) on the sensitivity to HT (44°C, 1 hour) in human retinoblastoma Y79 and WERI-Rb-1 cells by evaluating apoptosis and cell proliferation using flow cytometry, Western blotting, real-time quantitative polymerase chain reaction, and WST-8 assay. Furthermore, we investigated the effects of activating heat shock transcription factor 1 (HSF1) through a combination of PLK1 knockdown and HT using Western blotting and immunocytochemistry.
  
  
  RESULTS
  The combination of PLK1 inhibition and HT enhanced sensitivity to HT synergistically. Furthermore, PLK1 knockdown inhibited HT-induced phosphorylation of HSF1, the nuclear translocation of HSF1 from the cytoplasm, and nuclear granule formation of HSF1. Heat shock transcription factor 1, inactivated by the silencing of PLK1, reduced the expression of heat shock proteins (HSPs), such as HSP70 and HSP40, as well as the expression of Bcl-2-associated athanogene 3 (BAG3).
  
  
  CONCLUSIONS
  Polo-like kinase 1 inhibition may attenuate the thermoresistance of HT through the inactivation of HSF1 concomitant with reductions in HSPs and BAG3. The combination of PLK1 inhibition and HT may become an option for HT therapy in patients with retinoblastoma.
authors.affiliation: Department of Radiological Sciences, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Yunoki
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Tabuchi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hayashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Kondo
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D015153:Blotting, Western; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D049109:Cell Proliferation; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D055785:Gene Knockdown Techniques; D050956:HSP40 Heat-Shock Proteins / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D000076249:Heat Shock Transcription Factors; D006801:Humans; D006979:Hyperthermia, Induced; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D011621:Pteridines / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D019572:Retinal Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D012175:Retinoblastoma / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D000097869:Polo-Like Kinase 1
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D011621:Pteridines; D034741:RNA, Small Interfering; D014157:Transcription Factors; D000097869:Polo-Like Kinase 1; C414431:BAG3 protein, human; C518477:BI 2536; C000619706:HSF1 protein, human
keywords: HSF1; PLK1; hyperthermia; retinoblastoma