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

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
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DOI:
10.1002/jor.21056
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发表时间:
2010-06-01
影响因子:
2.8
通讯作者:
Kimura, Tomoatsu
Kimura, Tomoatsu
中科院分区:
医学3区
文献类型:
--
作者:
Hori, Takeshi;Kondo, Takashi;Kimura, Tomoatsu

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尽管骨肉瘤(OS)的化疗和手术治疗有所改进,但仍难以取得满意的结果。骨肉瘤的治疗需要开发新的治疗方法。研究了肿瘤坏死因子相关凋亡诱导配体(TRAIL)与电离辐射(IR)联合作用对人骨肉瘤细胞的影响。IR和TRAIL处理协同降低OS细胞系的细胞活力并增强凋亡。IR预处理增强TRAIL诱导的Bid和caspase-3激活。抗凋亡蛋白c-FLIP和MAP表达水平的降低也与凋亡增强相关。此外,IR预处理增强了转录阶段DR 4和DR 5的表达。这些结果可以成为未来使用TRAIL与IR治疗OS的基本证据线。(C)2009骨科研究学会。出版社:Wiley Periodicals,Inc. J Orthop Res 28:739-745,2010
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 MAP 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. (C) 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:739-745, 2010