Synergistic effect of panobinostat and bortezomib on chemoresistant acute myelogenous leukemia cells via AKT and NF-κB pathways
Synergistic effect of panobinostat and bortezomib on chemoresistant acute myelogenous leukemia cells via AKT and NF-κB pathways
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DOI：
10.1016/j.canlet.2012.07.030
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发表时间：
2012-12-30
期刊：
影响因子：
9.7
通讯作者：
Meng, Fan-Yi
中科院分区：
文献类型：
--
作者：
Jiang, Xue-Jie;Huang, Kai-Kai;Meng, Fan-Yi
在这项研究中，我们研究了帕比司他和硼替佐米对阿霉素耐药的HL60/ADR细胞和难治性急性髓性白血病（AML）原代细胞的协同作用。两种药物联合使用对这些细胞具有协同细胞毒性，并增加了HL60/ADR细胞对阿霉素的敏感性。Panobinostat联合硼替佐米可调节多种凋亡和药物代谢相关分子，包括半胱天冬酶的激活、XIAP的下调。Bcl-2和MRP1。这些作用可能是通过抑制AKT和nf - κ B途径介导的。这些发现为临床方案使用panobinostat和borezomib克服难治性AML患者的耐药提供了证据。2012爱思唯尔爱尔兰有限公司版权所有。
In this study, we investigated the synergistic effects of panobinostat and bortezomib on adriamycin-resistant HL60/ADR cells and refractory acute myelogenous leukemia (AML) primary cells. Combination of both agents had synergistic cytotoxicity on these cells, and increased the sensitivity of HL60/ADR cells to adriamycin. Panobinostat plus bortezomib was shown to modulate multiple apoptotic and drug metabolic related molecules, including activation of caspases, down-regulation of XIAP. Bcl-2 and MRP1. These effects were likely to be mediated via inhibition of AKT and NF-kappa B pathways. These findings provide evidence for clinic protocols using panobinostat and borezomib to overcome drug resistance in refractory AML patients. (c) 2012 Elsevier Ireland Ltd. All rights reserved.