Sensitization of resistant lymphoma cells to irradiation-induced apoptosis by the death ligand TRAIL
Sensitization of resistant lymphoma cells to irradiation-induced apoptosis by the death ligand TRAIL
复制标题
DOI：
10.1038/sj.onc.1204318
复制
发表时间：
2001-04-19
期刊：
影响因子：
8
通讯作者：
Budach, W
中科院分区：
文献类型：
--
作者：
Belka, C;Schmid, B;Budach, W
作用于不同死亡途径的抗肿瘤方法的组合似乎是增强治疗反应的理想选择，特别是当确定的耐药机制干扰个体细胞过程时。在 Jurkat 淋巴瘤细胞中分析了电离辐射 (XRT) 和死亡配体 TRAIL 触发的细胞凋亡途径。两者均诱导caspase-8、caspase-3、BID的激活和线粒体电位丧失，TRAIL诱导细胞凋亡需要caspase-8，而对于辐射诱导的细胞凋亡则不是必需的。 Bcl-2 对线粒体损伤的抑制消除了 XRT 诱导的细胞凋亡和 caspase 激活，但仅略微减弱了 TRAIL 诱导的细胞死亡。 TRAIL 和 XRT 联合处理在对照细胞中产生附加的凋亡效应，而在过表达 Bcl-2 的细胞中出现高度协同效应。此外，还发现 TRAIL 对辐射诱导的克隆细胞死亡有很强的作用。总之，TRAIL 与电离辐射联合治疗肿瘤似乎具有很高的潜在价值。
A combination of antitumor approaches acting on different death pathways seems ideal for increasing therapeutic responses, especially when defined resistance mechanisms interfere with individual cellular processes. Apoptosis pathways triggered by ionizing radiation (XRT) and the death ligand TRAIL were analysed in Jurkat lymphoma cells. Both induced the activation of caspase-8, caspase-3, BID and mitochondrial potential loss, TRAIL induced apoptosis required caspase-8, whereas it was not essential for radiation induced apoptosis. The inhibition of mitochondrial damage by Bcl-2 abrogated XRT induced apoptosis and caspase activation, but only marginally attenuated TRAIL induced cell death. The combined treatment with TRAIL and XRT exerted additive apoptotic effects in control cells, whereas highly synergistic effects occurred in cells overexpressing Bcl-2. In addition, a strong effect of TRAIL on radiation induced clonogenic cell death was found. In conclusion, TRAIL seems to be of high potential value for a combination with ionizing radiation in tumor therapy.