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• W2347780403 abstract "Objective Proteasome inhibitor have profound effects on tumor growth and cause cells to undergo apoptosis. PS-341,as an extremely potent and selective proteasome inhibitor,which is the first proteasome inhibitor to be used in clinical practice with the approve of FDA,can induces cell death via JNK pathway in vitro in glioma. However,suppressing proteasome complex by PS-341 may induce activation of heat shock factor1( HSF1),which can induce the expression of heat shock proteins( HSPs) to against cellular stress. In this study,we explored whether HSF1 could induce expression of HSPs and whether inhibition of HSF1 could enhance cell damage induced by PS-341 in glioma cells. Methods Surgically excised specimens from 30 patients with glioma( grade Ⅱ-Ⅳ) and10 normal brain control specimens obtained at autopsy were collected from the Department of Neurosurgery,The First Affiliated Hospital of Harbin Medical University,China. The histological characteristics of 30 patients with glioma were established based on World Health Organization( WHO) criteria.The collected tissues were immediately snap-frozen in liquid nitrogen and stored at-80℃ for Western blot analysis. Human U251 MG and A172 glioblastoma cell lines were obtained from the Japanese Cancer Research Resources Bank. Western was used to detect the expression of HSPs,HSF1 and the activation of JNK. HSF1 was knocked down by siRNA,then PS-341-induced cell damage was examined by Trypan blue exclusion assay and sub-G1 detection. Results HSP70 and HSF1 level were markedly higher in glioma tissues than in normal brain tissues. HSF1 knockdown significantly enhanced and prolonged JNK activation with strong inhibition of HSP70. HSP70 was strongly induced by PS-341 in HSF1 + / + cells,while PS-341 induced enhancement and prolongation of JNK activation in HSF1 –/– cells. Pretreatment by heat shock had no effect on cell viability of both cells and significantly antagonized PS-341-induced cell death in HSF1 + / + cells. Conclutions Our results demonstrated that HSF1 could induce expression of HSPs and inhibition of HSF1 could enhance cell damage induced by PS-341 in glioma cells. Administration of PS-341 in combination with either HSF1 inhibitor may act as a new approach to treatment of glioma." @default.
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• W2347780403 date "2014-01-01" @default.
• W2347780403 modified "2023-09-23" @default.
• W2347780403 title "Inhibition of heat shock factor1 response enhances PS-341-mediated glioma cell apoptosis" @default.
• W2347780403 hasPublicationYear "2014" @default.
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