顺铂通过上调 DR5 和下调 c-FLIP 恢复胶质母细胞瘤源性干细胞中的 TRAIL 凋亡途径。
Cisplatin restores TRAIL apoptotic pathway in glioblastoma-derived stem cells through up-regulation of DR5 and down-regulation of c-FLIP.
机构信息
Department of Hematology & Oncology, The First Hospital of Jilin University, Changchun, People's Republic of China.
出版信息
Cancer Invest. 2011 Oct;29(8):511-20. doi: 10.3109/07357907.2011.605412. Epub 2011 Aug 30.
Abstract
Glioblastoma-derived stem cells (GSCs) are responsible for the cancer resistance to therapies. We show here that GSC-enriched neurospheres are resistant to the treatment of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) due to the insufficient expression of the death receptor DR4 and DR5 and the overexpression of cellular Fas-associated death domain-like interleukin-1β-converting enzyme-inhibitory protein (c-FLIP). However, treatment with cisplatin leads to the upregulation of DR5 and downregulation of c-FLIP and restores TRAIL apoptotic pathway in the neurospheres. This study suggests that the combined treatment of TRAIL and cisplatin can induce apoptosis in GSCs and thus provide an effective treatment of glioblastomas.
摘要
胶质母细胞瘤干细胞（GSCs）是导致癌症对治疗产生耐药性的原因。我们在这里表明，由于死亡受体 DR4 和 DR5 的表达不足以及细胞 Fas 相关死亡域样白细胞介素-1β转换酶抑制蛋白（c-FLIP）的过表达，富含 GSC 的神经球对肿瘤坏死因子相关凋亡诱导配体（TRAIL）的治疗具有抗性。然而，顺铂治疗导致 DR5 的上调和 c-FLIP 的下调，并在神经球中恢复 TRAIL 凋亡途径。这项研究表明，TRAIL 和顺铂的联合治疗可以诱导 GSCs 凋亡，从而为胶质母细胞瘤的治疗提供有效手段。
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DR5-mediated DISC controls caspase-8 cleavage and initiation of apoptosis in human glioblastomas.DR5 介导的 DISC 控制人胶质母细胞瘤中 caspase-8 的切割和凋亡的起始。
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