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电离辐射通过上调人骨肉瘤细胞中的死亡受体 4(DR4)和死亡受体 5(DR5)增强肿瘤坏死因子相关凋亡诱导配体(TRAIL)诱导的细胞凋亡。

Ionizing radiation enhances tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis through up-regulations of death receptor 4 (DR4) and death receptor 5 (DR5) in human osteosarcoma cells.

机构信息

Department of Radiological Sciences, Graduate School of Medicine and Pharmaceutical Science, University of Toyama, Toyama-city, Toyama, Japan.

出版信息

J Orthop Res. 2010 Jun;28(6):739-45. doi: 10.1002/jor.21056.

DOI:10.1002/jor.21056
PMID:20041491
Abstract

Despite improvements in chemotherapy and surgery in the treatment of osteosarcoma (OS), satisfactory results are still difficult to achieve. Novel therapeutic modalities need to be developed for osteosarcoma treatment. The combined effects of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and ionizing radiation (IR) on human OS cells were investigated. IR and TRAIL treatment synergistically decreased the cell viability and enhanced apoptosis in OS cell lines. IR pretreatment enhances TRAIL-induced Bid and caspase-3 activations. Decreases in the expression levels of the antiapoptotic proteins c-FLIP and XIAP also associated with apoptosis enhancement. Furthermore, IR pretreatment enhanced DR4 and DR5 expressions at the transcription stage. These results can become the basic lines of evidence for the future treatment of OS using TRAIL with IR.

摘要

尽管在骨肉瘤(OS)的化疗和手术治疗方面取得了进展,但仍难以达到满意的效果。需要开发新的治疗方法来治疗骨肉瘤。研究了肿瘤坏死因子相关凋亡诱导配体(TRAIL)和电离辐射(IR)联合对人骨肉瘤细胞的作用。IR 和 TRAIL 治疗协同降低了骨肉瘤细胞系的细胞活力并增强了细胞凋亡。IR 预处理增强了 TRAIL 诱导的 Bid 和 caspase-3 的激活。凋亡增强也与抗凋亡蛋白 c-FLIP 和 XIAP 的表达水平降低有关。此外,IR 预处理增强了转录阶段 DR4 和 DR5 的表达。这些结果可以为未来使用 TRAIL 和 IR 治疗骨肉瘤提供基础依据。

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