The piperidine nitroxide Tempol potentiates the cytotoxic effects of temozolomide in human glioblastoma cells.
The piperidine nitroxide Tempol potentiates the cytotoxic effects of temozolomide in human glioblastoma cells.
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哌啶硝基氧 Tempol 增强替莫唑胺对人胶质母细胞瘤细胞的细胞毒性作用。
DOI：
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发表时间：
2004
影响因子：
5.2
通讯作者：
M. Gariboldi
中科院分区：
文献类型：
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作者：
R. Ravizza;E. Cereda;E. Monti;M. Gariboldi
替莫唑胺(TMZ)是一种甲基化药物，在治疗黑色素瘤和中级胶质瘤方面具有良好的抗肿瘤疗效。不幸的是，它在治疗高级别胶质瘤(胶质母细胞瘤)中的应用受到多方面耐药机制的限制。本研究的目的是评价TMZ对两种人脑胶质母细胞瘤细胞株U87 MG和U373 MG的细胞毒作用。TPL是一种低相对分子质量的哌啶氮氧化物，可抑制小鼠脑胶质瘤细胞的体内外生长。为此，我们使用了两种不同的联合暴露于两种制剂的时间表。我们的数据表明，在两个测试方案中，TPL与TMZ在U87 MG和U373 MG细胞中都有协同作用。伴随着这种效应的是细胞凋亡性增加，以及参与细胞凋亡过程控制的基因表达的变化。还观察到TPL诱导GSH水平和GSH相关酶活性的细胞型特异性降低，这可能有助于其增敏作用。
Temozolomide (TMZ) is a methylating agent with promising antitumor efficacy for the treatment of melanomas and intermediate-grade gliomas. Unfortunately, its use in the management of high-grade gliomas (glioblastomas) is limited by multifaceted resistance mechanisms. The aim of this study was to evaluate the possibility to improve the cytotoxic response of two human glioblastoma cell lines, U87MG and U373MG, to TMZ by the use of Tempol (TPL), a low molecular weight piperidine nitroxide that has been shown to inhibit in vitro and in vivo growth of murine glioma cells. To this purpose, we used two different schedules for the combined exposure to the two agents. Our data indicate that TPL synergizes with TMZ in both U87MG and U373MG cells for both schedules tested. This effect is accompanied by an increase in apoptotic cell death and by changes in the expression of genes involved in control of the apoptotic process. TPL was also observed to induce a cell-type specific decrease in GSH levels and in GSH-related enzyme activities that could contribute to its sensitizing effect.