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首页> 外文期刊>Cellular Physiology and Biochemistry >Role of Na+/Ca2+ Exchangers in Therapy Resistance of Medulloblastoma Cells
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Role of Na+/Ca2+ Exchangers in Therapy Resistance of Medulloblastoma Cells

机译：Na + / Ca2 +交换子在髓母细胞瘤细胞治疗抗性中的作用

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>Background/Aims: Alterations of cytosolic Ca2+-activity ([Ca2+]i) are decisive in the regulation of tumor cell proliferation, migration and survival. Transport processes participating in the regulation of [Ca2+]i include Ca2+ extrusion through K+-independent (NCX) and/or K+-dependent (NCKX) Na+/Ca2+-exchangers. The present study thus explored whether medulloblastoma cells express Na+/Ca2+-exchangers, whether expression differs between therapy sensitive D283 and therapy resistant UW228-3 medulloblastoma cells, and whether Na+/Ca2+-exchangers participate in the regulation of cell survival. Methods: In therapy sensitive D283 and therapy resistant UW228-3 medulloblastoma cells transcript levels were estimated by RT-PCR, protein abundance by Western blotting, cytosolic Ca2+-activity ([Ca2+]i) from Fura-2-fluorescence, Na+/ Ca2+-exchanger activity from the increase of [Ca2+]i (?”[Ca2+]i) and from whole cell current (Ica) following abrupt replacement of Na+ containing (130 mM) and Ca2+ free by Na+ free and Ca2+ containing (2 mM) extracellular perfusate as well as cell death from PI -staining and annexin-V binding in flow cytometry. Results: The transcript levels of NCX3, NCKX2, and NCKX5, protein abundance of NCX3, slope and peak of ?”[Ca2+]i as well as Ica were significantly lower in therapy sensitive D283 than in therapy resistant UW228-3 medulloblastoma cells. The Na+/Ca2+-exchanger inhibitor KB-R7943 (10 ?μM) significantly blunted ?”[Ca2+]i, and augmented the ionizing radiation-induced apoptosis but did not significantly modify clonogenicity of medulloblastoma cells. Apoptosis was further enhanced by NCX3 silencing. Conclusions: Na+/Ca2+-exchanger activity significantly counteracts apoptosis but does not significantly affect clonogenicity after radiation of medulloblastoma cells.
机译：> 背景/目标： 胞质Ca 2 + -活性（[Ca 2 + ] < sub> i ）在调节肿瘤细胞的增殖，迁移和存活中起决定性作用。参与[Ca 2 + ] i 调控的运输过程包括通过K + -挤出的Ca 2 + 独立（NCX）和/或K + 依赖（NCKX）Na + / Ca 2 + 交换器。因此，本研究探讨了髓母细胞瘤细胞是否表达Na + / Ca 2 + 交换子，对治疗敏感的D283和对治疗耐药的UW228-3髓母细胞瘤细胞之间的表达是否不同以及是否Na + / Ca 2 + 交换子参与细胞存活的调控。 方法： 在具有治疗敏感性的D283和具有抗药性的UW228-3髓母细胞瘤细胞中，通过RT-PCR估算转录水平，通过蛋白质印迹法测定蛋白质丰度，胞浆Ca 2+来自Fura-2-荧光的-活性（[Ca 2 + ] i ），Na + / Ca 2 [ 2 + ] i （？” [Ca 2 + ] i ）和突然替换含有（130 mM）和Ca 2 + 的全细胞电流（I ca ） >游离的Na + 和Ca 2 + 含（2 mM）细胞外灌注液，以及流式细胞术中PI染色和膜联蛋白V结合引起的细胞死亡。 结果： NCX3，NCKX2和NCKX5的转录水平，NCX3的蛋白质丰度，？” [Ca 2 + ]的斜率和峰值在对治疗敏感的D283中， i 和I ca 显着低于对治疗具有抵抗力的UW228-3髓母细胞瘤细胞。 Na + / Ca 2 + 交换抑制剂KB-R7943（10？M）明显钝化？” [Ca 2 + ] i ，并增加了电离辐射诱导的细胞凋亡，但并未显着改变髓母细胞瘤细胞的克隆形成能力。 NCX3沉默进一步增强了细胞凋亡。 结论： Na + / Ca 2 + 交换子的活性显着抵消细胞凋亡，但对辐射后的克隆形成能力没有明显影响髓母细胞瘤细胞。

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