Comparative proteome study of apoptosis induced by As4S4 in retinoid acid resistant human acute promyelocytic leukemia NB4-R1 cells
Comparative proteome study of apoptosis induced by As4S4 in retinoid acid resistant human acute promyelocytic leukemia NB4-R1 cells
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As4S4诱导视黄酸耐药人急性早幼粒细胞白血病NB4-R1细胞凋亡的比较蛋白质组研究
DOI：
10.1016/j.leukres.2010.03.038
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发表时间：
2010-11-01
影响因子：
2.7
通讯作者：
Zhang, Mei
中科院分区：
文献类型：
--
作者：
Qi, Jun;He, Pengcheng;Zhang, Mei
与三氧化二砷相比，四硫化四砷（As 4S 4）的毒性有所改善，是新的口服砷制剂的基本成分，该制剂在治疗新诊断的急性早幼粒细胞白血病（APL）和更重要的复发/难治性APL方面都非常有效和安全。虽然研究表明As 4S 4的治疗作用与其诱导细胞凋亡密切相关，但As 4S 4治疗APL的系统分子机制仍不清楚。本研究首先对As 4S 4的细胞毒作用和细胞凋亡证据进行了一系列体外实验研究，然后利用高分辨双向电泳和质谱技术对As 4S 4诱导的RA耐药细胞凋亡蛋白质组进行了系统的鉴定和分析。其中，调控靶蛋白SET、RPP 2和PHB的表达和功能可能成为RA耐药APL潜在的有效治疗策略。本研究不仅有助于从整体上了解As 4S 4诱导RA耐药APL细胞凋亡的信号转导机制，而且对筛选治疗造血系统恶性肿瘤的药物靶点具有重要意义。(C)2010爱思唯尔有限公司版权所有。
Tetra-arsenic tetra-sulfide (As4S4), with improved toxicity profiles relative to arsenic trioxide, is the essential component of the new oral arsenic formulation which is highly effective and safe in the treatment of both newly diagnosed acute promyelocytic leukemia (APL) and more importantly relapsed/refractory APL. Although it is investigated that the therapeutic action of As4S4 is closely associated with its induced cells apoptosis, the definitive systematic molecular mechanism of action of As4S4 in APL therapy is still remained unknown. In this study, a serial of assays in vitro about the cytotoxicity of As4S4 and cellular apoptotic evidences were done, then a proteomic investigation with the high-resolution two-dimensional electrophoresis system and mass spectrometry were performed to obtain for the first time systematic identification and characterization of the global proteome of apoptosis induced by As4S4 in retinoic acid (RA)-resistant cells. Among them, expressional and functional regulations of target proteins SET, RPP2 and PHB might be the potential novel effective therapeutic strategies for RA-resistant APL. This study will not only facilitate to understand the signal transduction of apoptosis of RA-resistant APL cells induced by As4S4 as a whole, but also is important to screen for drug targets as a new therapeutic strategy for hematopoietic malignant tumors. (C) 2010 Elsevier Ltd. All rights reserved.