帕比司他和马利司他在急性髓系白血病和硼替佐米耐药模型中的疗效。
Efficacy of panobinostat and marizomib in acute myeloid leukemia and bortezomib-resistant models.
机构信息
Department of Pediatrics Research, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 0853, Houston, TX 77030, USA; Division of Pediatric Hematology-Oncology, Department of Pediatrics. University of Miami-Miller School of Medicine, Miami, FL 33136.
Department of Pediatrics Research, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 0853, Houston, TX 77030, USA; The University of Texas Graduate School of Biomedical Sciences at Houston, The University of Texas MD Anderson Cancer Center, 6767 Bertner Avenue, Houston, TX 77030, USA.
出版信息
Leuk Res. 2015 Mar;39(3):371-9. doi: 10.1016/j.leukres.2014.12.014. Epub 2015 Jan 3.
Current relapse rates in acute myeloid leukemia (AML) highlight the need for new therapeutic strategies. Panobinostat, a novel pan-histone deacetylase inhibitor, and marizomib, a second-generation proteasome inhibitor, are emerging as valuable therapeutic options for hematological malignancies. Here we evaluated apoptotic effects of this combinatorial therapy in AML models and report earlier and higher reactive oxygen species induction and caspase-3 activation and greater caspase-8 dependence than with other combinations. In a bortezomib refractory setting, panobinostat induced high levels of DNA fragmentation, and its action was significantly augmented when combined with marizomib. These data support further study of this combination in hematological malignancies.
目前急性髓系白血病（AML）的复发率凸显出新的治疗策略的必要性。帕比司他，一种新型的组蛋白去乙酰化酶抑制剂，和马利昔单抗，第二代蛋白酶体抑制剂，作为血液恶性肿瘤的有价值的治疗选择正在出现。在这里，我们评估了这种联合治疗在 AML 模型中的凋亡作用，并报告了比其他组合更早、更高的活性氧诱导和 caspase-3 激活，以及更大的 caspase-8 依赖性。在硼替佐米耐药的情况下，帕比司他诱导高水平的 DNA 片段化，当与马利昔单抗联合使用时，其作用显著增强。这些数据支持在血液恶性肿瘤中进一步研究这种联合用药。
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