首页> 外文期刊>The Korean Journal of Physiology & Pharmacology >Role of Caveolin-1 in Indomethacin-induced Death of Human Hepatoadenocarcinoma SK-Hep1 Cells
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Role of Caveolin-1 in Indomethacin-induced Death of Human Hepatoadenocarcinoma SK-Hep1 Cells

机译:Caveolin-1在吲哚美辛诱导的人肝腺癌SK-Hep1细胞死亡中的作用

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Caveolin-1 (CAV1) is an integral membrane protein that may function as a scaffold for plasma membrane proteins and acts as a tumor suppressor protein. One causative factor of chemotherapy-resistant cancers is P-plycoprotein (P-gp), the product of the multidrug resistance-1 gene ( MDR1 ), which is localized in the caveolar structure. Currently, the interactive roles of CAV1 and MDR1 expression in the death of cancer cells remain controversial. In this study, we investigated the effects of indomethacin on the cell viability and the expression levels of MDR1 mRNA and protein in a CAV1-siRNA-mediated gene knockdown hepatoma cell line (SK-Hep1). Cell viability was significantly decreased in CAV1-siRNA-transfected cells compared with that of control-siRNA-transfected cells. Furthermore, the viability of cells pretreated with CAV1 siRNA was markedly decreased by treatment with indomethacin (400μM for 24 h). However, the protein and mRNA levels of MDR1 were unchanged in CAV1-siRNA-transfected cells. These results suggest that CAV1 plays an important role as a major survival enzyme in cancer cells, and indomethacin can sensitively induce cell death under conditions of reduced CAV1 expression, independent of MDR1 expression.
机译:Caveolin-1(CAV1)是不可或缺的膜蛋白,可以充当质膜蛋白的支架,并起抑癌蛋白的作用。化疗耐药性癌症的一个致病因素是P-糖蛋白(P-gp),它是多药耐药性1基因(MDR1)的产物,它位于小窝结构中。目前,CAV1和MDR1表达在癌细胞死亡中的交互作用仍存在争议。在这项研究中,我们调查了吲哚美辛对CAV1-siRNA介导的基因敲除肝癌细胞系(SK-Hep1)细胞活力以及MDR1 mRNA和蛋白质表达水平的影响。与对照siRNA转染的细胞相比,CAV1-siRNA转染的细胞的细胞活力显着降低。此外,用消炎痛(400μM,24 h)处理后,用CAV1 siRNA预处理的细胞的活力显着降低。但是,在CAV1-siRNA转染的细胞中,MDR1的蛋白质和mRNA水平没有变化。这些结果表明,CAV1作为癌细胞中的主要生存酶发挥着重要作用,并且吲哚美辛可以在CAV1表达降低的条件下(独立于MDR1表达)敏感地诱导细胞死亡。

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