Reference - Detail
|Author||Yunoki T, Tabuchi Y, Hayashi A, Kondo T.|
|Title||Inhibition of polo-like kinase 1 promotes hyperthermia sensitivity via inactivation of heat shock transcription factor 1 in human retinoblastoma cells.|
|Journal||Invest. Ophthalmol. Vis. Sci.|
PURPOSE: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.
|MeSH||Adaptor Proteins, Signal Transducing / metabolism Apoptosis Apoptosis Regulatory Proteins Blotting, Western Cell Cycle Cell Cycle Proteins / antagonists & inhibitors* Cell Cycle Proteins / genetics Cell Proliferation Cell Survival DNA-Binding Proteins / metabolism* Enzyme Inhibitors / pharmacology Flow Cytometry Gene Knockdown Techniques HSP40 Heat-Shock Proteins / metabolism HSP70 Heat-Shock Proteins / metabolism Heat Shock Transcription Factors Humans Hyperthermia, Induced* Phosphorylation Protein-Serine-Threonine Kinases / antagonists & inhibitors* Protein-Serine-Threonine Kinases / genetics Proto-Oncogene Proteins / antagonists & inhibitors* Proto-Oncogene Proteins / genetics Pteridines / pharmacology RNA, Small Interfering / genetics Real-Time Polymerase Chain Reaction Retinal Neoplasms / metabolism Retinal Neoplasms / pathology Retinal Neoplasms / therapy* Retinoblastoma / metabolism Retinoblastoma / pathology Retinoblastoma / therapy* Transcription Factors / metabolism* Tumor Cells, Cultured|
|Human and Animal Cells|