Fucoidan enhances the therapeutic potential of arsenic trioxide and all-trans retinoic acid in acute promyelocytic leukemia, in vitro and in vivo.
Fucoidan enhances the therapeutic potential of arsenic trioxide and all-trans retinoic acid in acute promyelocytic leukemia, in vitro and in vivo.
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DOI：
10.18632/oncotarget.10016
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发表时间：
2016-07-19
期刊：
影响因子：
--
通讯作者：
Woods GM
中科院分区：
文献类型：
--
作者：
Atashrazm F;Lowenthal RM;Dickinson JL;Holloway AF;Woods GM
目前治疗急性早幼粒细胞白血病(APL)的发病率和死亡率仍然是一个重要的临床问题，尽管患者的存活率有所改善。因此，开发在提高疗效的同时降低发病率的辅助疗法是重要的。减少辅助治疗中有毒药物的浓度有可能减少不良副作用。因此，本研究旨在确定抗肿瘤药物岩藻糖胶与现有APL治疗方法的协同作用。治疗剂量和亚治疗剂量的岩藻糖胶联合ATO和ATRA作用于体外培养的人APL细胞株NB4，可见亚G0/G1期细胞增多，Annexin V/PI阳性凋亡细胞增多，DNA片段化。CD11b的表达增加表明，这种增殖减少和凋亡增加伴随着髓系分化的增强。在AML细胞系Kasumi-1中没有观察到这一点，这表明APL具有特异性。用岩藻糖胶+全反式维甲酸或岩藻糖胶+ATO治疗荷瘤小鼠，可延缓肿瘤生长，诱导分化，延长肿瘤体积倍增时间。在岩藻糖胶+全反式维甲酸处理的小鼠中，从切除的肿瘤块中分化出的APL细胞CD44表达降低。这可能会导致APL患者细胞迁移减少。我们的发现为使用岩藻糖胶作为辅助治疗APL提供了证据。
The morbidity and mortality associated with current therapies for acute promyelocytic leukemia (APL) remain a significant clinical concern, despite improvements in patient survival. Consequently, the development of adjuvant therapies that increase efficacy while reducing morbidities is important. Reducing the concentration of the toxic drugs in adjuvant therapy has the potential to reduce unwanted side effects. Therefore, this study aimed to determine the synergistic effects of fucoidan, an anti-tumor agent, with current APL therapies. When the human APL cell line, NB4, was treated in vitro with fucoidan plus ATO and ATRA at therapeutic and sub-therapeutic doses, there was an increase in sub-G0/G1 cells, annexin V/PI-positive-apoptotic cells and DNA fragmentation. This reduction in proliferation and increase in apoptosis was accompanied by enhanced myeloid differentiation as indicated by an increased expression of CD11b. This was not observed with the AML cell line Kasumi-1, suggesting specificity for APL. In vivo treatment of APL-bearing mice with fucoidan+ATRA or fucoidan+ATO delayed tumor growth, induced differentiation and increased tumor volume doubling time. The differentiated APL cells derived from the excised tumor mass exhibited decreased CD44 expression in fucoidan+ATRA treated mice. This could translate to decreased cell migration in APL patients. Our findings provide evidence supporting the use of fucoidan as an adjuvant therapeutic agent in the treatment of APL.
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影响因子：
45.3
作者：
AdeS, Lionel;Chevret, Sylvie;Fenaux, Pierre
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