内质网应激诱导剂，但不是伊马替尼，可增强费城染色体阳性白血病细胞对 TRAIL 介导的凋亡的敏感性。
Endoplasmic reticulum stress inducers, but not imatinib, sensitize Philadelphia chromosome-positive leukemia cells to TRAIL-mediated apoptosis.
机构信息
Department of Pediatrics, School of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 409-3898, Japan.
出版信息
Leuk Res. 2011 Jul;35(7):940-9. doi: 10.1016/j.leukres.2011.03.016. Epub 2011 Apr 3.
Philadelphia-chromosome (Ph1)-positive leukemia cells frequently express death receptors DR4/DR5 for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and show high TRAIL-sensitivity. It has been reported that imatinib damaged cardiomyocytes by triggering endoplasmic reticulum (ER) stress and that ER stress inducers intensified TRAIL-sensitivity of some cancer cells by upregulating DR4/DR5 expression. In fact, ER stress inducers enhanced TRAIL-sensitivity of Ph1-positive leukemia cells by upregulating DR4/DR5 expression. In contrast, imatinib did not induce ER stress responses and unexpectedly downregulated DR4/DR5 expression, indicating that sensitization of Ph1-positive leukemia cells to TRAIL-mediated cellular immunity by imatinib through upregulation of DR4/DR5 expression is unlikely.
费城染色体（Ph1）阳性白血病细胞常表达肿瘤坏死因子相关凋亡诱导配体（TRAIL）的死亡受体 DR4/DR5，表现出对 TRAIL 的高敏感性。据报道，伊马替尼通过触发内质网（ER）应激损伤心肌细胞，而 ER 应激诱导剂通过上调 DR4/DR5 的表达增强了某些癌细胞对 TRAIL 的敏感性。事实上，ER 应激诱导剂通过上调 DR4/DR5 的表达增强了 Ph1 阳性白血病细胞对 TRAIL 的敏感性。相比之下，伊马替尼并没有诱导 ER 应激反应，反而意外地下调了 DR4/DR5 的表达，表明伊马替尼通过上调 DR4/DR5 的表达增强 Ph1 阳性白血病细胞对 TRAIL 介导的细胞免疫的敏感性不太可能。
Zotero 插件