• pu-h71 effectively induces degradation of iκb kinase β in the presence of tnf-α

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    جزئیات بیشتر مقاله
    • تاریخ ارائه: 1392/07/24
    • تاریخ انتشار در تی پی بین: 1392/07/24
    • تعداد بازدید: 801
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     this study is to determine if pu-h71, a heat shock protein inhibitor, induces killing of malignant breast cells together with treatment of tumor necrosis factor-α (tnf-α). the related molecular mechanisms were also studied. a primary mammary epithelial cell line hmec2595 cells and the highly metastatic breast cell line mda-mb-231, the her2-positive bt-474 cells, and the er-positive mcf7 cells were treated with pu-h71 in the presence or absence of tnf-α. the effects of pu-h71 and tnf-α treatments on cells viabilities and on intracellular signaling pathway proteins were determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, apoptosis assays, immunoblot assays, and luciferase assays. it was found that tnf-α enhances the toxic effects of pu-h71 on tumor cells but not normal cells. pu-h71 treatments lead to degradation of ikkβ. moreover, pu-h71 down-regulates the nf-κb transcriptional activity induced by tnf-α treatment. the experimental results indicated pu-h71 effectively induces cell killing of malignant breast cells in the presence of tnf-α, possibly through a mechanism related to degradation of ikkβ. it is suggested that combination of pu-h71 and tnf-α treatments might be an effective therapeutic strategy of breast malignancies.

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