Chang Yu-Chien, Lo Wen-Jyi, Huang Yu-Ting, Lin Chaio-Lin, Feng Chiu-Che, Lin Hsin-Ting, Cheng Hsu-Chen, Yeh Su-Peng
a Department of Medical Research , Stem Cell Research Lab., China Medical University Hospital , Taichung , Taiwan.
b Department of Life Science , National Chung Hsing University , Taichung , Taiwan.
Leuk Lymphoma. 2017 Sep;58(9):1-12. doi: 10.1080/10428194.2017.1280604. Epub 2017 Jan 31.
Deferasirox (DFX), in addition to its iron-chelation property, has marked anti-proliferative effects on cancer cells. However, the activity and mechanism by which DFX inhibits acute myeloid leukemia (AML) cells remain to be elucidated. Furthermore, the anti-leukemia effect of combining DFX with currently recommended agents doxorubicin (DOX) and cytosine arabinoside (Ara-C) has not been studied. In this study, we show that DFX significantly reduces the viability of three AML cell lines, HL60, THP1, and WEHI3 and two primary leukemic cells harvested from AML patients. DFX induces cell cycle arrest at G1 phase and apoptosis and inhibits phosphorylation of ERK. We also showed that DFX antagonizes the anti-leukemic effect of DOX. On the contrary, combining DFX with Ara-C created a synergistic effect. Our study confirms the anti-leukemia activity of DFX and provides important information on how to select a partner drug for DFX for the treatment of AML in future clinical trials.
地拉罗司（DFX）除具有铁螯合特性外，对癌细胞还具有显著的抗增殖作用。然而，DFX抑制急性髓系白血病（AML）细胞的活性及机制仍有待阐明。此外，DFX与目前推荐的药物阿霉素（DOX）和阿糖胞苷（Ara-C）联合使用的抗白血病效果尚未得到研究。在本研究中，我们发现DFX可显著降低三种AML细胞系HL60、THP1和WEHI3以及从AML患者采集的两种原代白血病细胞的活力。DFX诱导细胞周期停滞于G1期并引发凋亡，同时抑制ERK的磷酸化。我们还发现DFX可拮抗DOX的抗白血病作用。相反，DFX与Ara-C联合使用则产生协同效应。我们的研究证实了DFX的抗白血病活性，并为未来临床试验中如何为DFX选择联合用药以治疗AML提供了重要信息。
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