Synergistic inhibitory effects of deferasirox in combination with decitabine on leukemia cell lines SKM-1, THP-1, and K-562.
Synergistic inhibitory effects of deferasirox in combination with decitabine on leukemia cell lines SKM-1, THP-1, and K-562.
复制标题
地拉罗司联合地西他滨对白血病细胞系 SKM-1、THP-1 和 K-562 的协同抑制作用
DOI：
10.18632/oncotarget.16583
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发表时间：
2017-05-30
期刊：
影响因子：
--
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Li N;Chen Q;Gu J;Li S;Zhao G;Wang W;Wang Z;Wang X
法国骨髓增生异常综合征(MDS)小组的一项多中心研究证实，铁络合疗法是一个独立的预后因素，可以提高患有输血依赖型低风险MDS患者的存活率。在本研究中，我们旨在通过研究铁络合剂去铁西洛(DFX)和DNA甲基转移酶抑制剂地西他滨(DAC)对白血病细胞株SKM-1、THP-1和K-562的协同作用，在体外探讨这一临床现象。DFX或DAC均可促进这三种细胞系的细胞凋亡、诱导细胞周期停滞和抑制增殖。DFX和DAC联合使用的效果比单独使用任何一种药物的效果要大得多。DFX与DAC对三种细胞株的细胞凋亡均有协同作用，对K-562细胞的G0/G1期细胞周期有明显的抑制作用。DFX可不同程度地降低ROS水平。相比之下，DAC增加了ROS水平，当两种药物联合使用时，ROS也被注意到增加。DAC处理细胞可能通过去甲基化诱导ABAT、APAF-1、FADD、HJV和SMPD3的重新表达。而DAC与DFX联用仅对HJV的再表达有较强的协同作用。
A multi-center study from the French Myelodysplastic Syndrome (MDS) Group confirmed that iron chelation therapy is an independent prognostic factor that can increase the survival rate of patients who are suffering from transfusion-dependent low-risk MDS. In this study, we aimed to explore this clinical phenomena in vitro, by exploring the synergistic effect of the iron chelator Deferasirox (DFX) and the DNA methyl transferase inhibitor Decitabine (DAC) in the leukemia cell lines SKM-1, THP-1, and K-562. Treatment with both DFX or DAC promoted apoptosis, induced cell cycle arrest, and inhibited proliferation in all three of these cell lines. The combination of DFX and DAC was much greater than the effect of using either drug alone. DFX showed a synergistic effect with DAC on cell apoptosis in all three cell lines and on cell cycle arrest at the G0/G1 phase in K-562 cells. DFX decreased the ROS levels to varying degrees. In contrast, DAC increased ROS levels and an increase in ROS was also noted when the two drugs were used in combination. Treatment of cells with DAC induced re-expression of ABAT, APAF-1, FADD, HJV, and SMPD3, presumably through demethylation. However the combination of DAC and DFX just had strong synergistic effect on the re-expression of HJV.