論文 - 詳細
RRC ID | 38328 |
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著者 | Song X, Chen Z, Wu C, Zhao S. |
タイトル | Abrogating HSP response augments cell death induced by As2O3 in glioma cell lines. |
ジャーナル | Can J Neurol Sci |
Abstract |
OBJECTIVES:We previously reported that Arsenic trioxide (ATO) can inhibit glioma growth both in vitro and in vivo. While the use of ATO alone for solid tumor treatment sometimes was found to be ineffective which may be due to the protective pathways including heat shock proteins (HSPs) response induced by ATO. In this study, we modified HSPs expression to investigate whether HSPs had some effect on ATO induced glioma cell death. METHODS:Trypan bule exclusion assay, mitochondrial membrane potential (MMP) Assay, and SubG1 detection were used to evaluate cell viability and western-blot was employed to detect HSPs and some apoptosis markers expression induced by ATO. Heat pre-treatment, HSPs inhibitor, or Heat Shock factor-1 (HSF1) knockdown by SiRNA was employed to modify HSPs levels. RESULTS:It was showed that KNK437 (HSPs inhibitor) or HSF1 knockdown significantly enhanced cell death, MMP disruption, JNK phosphorylation and caspase-3 cleavage induced by ATO, which was accompanied by abrogation of HSPs induction, while heat pre-treatment with clear HSPs induction had strong protection on the effects mentioned above. CONCLUSION:Those data suggested that HSPs play protective roles on ATO induced cell death in glioma. Inhibition of HSPs may have a synergistic effect with ATO on glioma treatment. |
巻・号 | 37(4) |
ページ | 504-11 |
公開日 | 2010-7-1 |
DOI | 10.1017/s0317167100010544 |
PII | 768272552G406501 |
PMID | 20724260 |
MeSH | Antineoplastic Agents / pharmacology* Arsenic Trioxide Arsenicals / pharmacology* Benzhydryl Compounds / pharmacology Caspase 3 / metabolism Cell Death / drug effects Cell Line, Tumor DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism Dose-Response Relationship, Drug Drug Interactions Enzyme Inhibitors / pharmacology Flow Cytometry / methods Gene Expression Regulation / drug effects* Gene Expression Regulation, Neoplastic / drug effects* Glioma / pathology* Heat Shock Transcription Factors Heat-Shock Proteins / genetics Heat-Shock Proteins / metabolism* Heat-Shock Response / drug effects Heat-Shock Response / physiology Humans MAP Kinase Kinase 4 / metabolism Membrane Potential, Mitochondrial / drug effects Oxides / pharmacology* Pyrrolidinones / pharmacology RNA, Small Interfering / pharmacology Time Factors Transcription Factors / genetics Transcription Factors / metabolism Trypan Blue |
IF | 1.714 |
引用数 | 11 |
WOS 分野 | CLINICAL NEUROLOGY |
リソース情報 | |
ヒト・動物細胞 | T98G(RCB1954) A549(RCB0098) |