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硼替佐米和帕比司他通过 AKT 和 NF-κB 通路对耐药性急性髓系白血病细胞的协同作用。

Synergistic effect of panobinostat and bortezomib on chemoresistant acute myelogenous leukemia cells via AKT and NF-κB pathways.

机构信息

Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

出版信息

Cancer Lett. 2012 Dec 30;326(2):135-42. doi: 10.1016/j.canlet.2012.07.030. Epub 2012 Aug 1.

DOI:10.1016/j.canlet.2012.07.030
PMID:22863538
Abstract

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-κB pathways. These findings provide evidence for clinic protocols using panobinostat and borezomib to overcome drug resistance in refractory AML patients.

摘要

在这项研究中，我们研究了帕比司他和硼替佐米联合应用对阿霉素耐药 HL60/ADR 细胞和难治性急性髓系白血病（AML）原代细胞的协同作用。这两种药物联合应用对这些细胞具有协同细胞毒性作用，并增加了 HL60/ADR 细胞对阿霉素的敏感性。帕比司他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、Bcl-2 和 MRP1 的下调。这些作用可能是通过抑制 AKT 和 NF-κB 通路介导的。这些发现为临床方案提供了依据，即使用帕比司他和硼替佐米来克服难治性 AML 患者的耐药性。

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