Department of Biochemistry, School of Medicine, Shantou University, Shantou, Guangdong, China.
Leuk Lymphoma. 2010 Feb;51(2):297-303. doi: 10.3109/10428190903486212.
Arsenic trioxide (ATO) is an effective therapeutic agent for acute promyelocytic leukemia (APL) and other hematopoietic malignancies. We found that ATO down-regulated the global DNA methylation level in HL-60 cells with high-performance capillary electrophoresis (HPCE) assay. Using combination index method of Chou and Talalay, interactions between ATO and epigenetic therapeutic agents were analyzed in three human leukemia cell lines (HL-60, U937, and K562). A synergistic interaction was observed in HL-60 cells between ATO and 5-Aza-2'-Deoxycytidine (DAC), while an antagonistic interaction was found in U937 cells between ATO and valproic acid (VPA). The combination of ATO with trichostatin A (TSA) caused an antagonistic interaction in U937 and K562 cells. These results not only highlight possible diversity of the anti-leukemia mechanisms of ATO, but also provide initial guide for further investigation of leukemia therapies based on the combination of ATO with epigenetic agents.
三氧化二砷（ATO）是治疗急性早幼粒细胞白血病（APL）和其他血液系统恶性肿瘤的有效药物。我们发现 ATO 通过高效毛细管电泳（HPCE）检测降低了 HL-60 细胞的全基因组 DNA 甲基化水平。采用 Chou 和 Talalay 的联合指数方法，分析了 ATO 与三种人白血病细胞系（HL-60、U937 和 K562）中表观遗传治疗药物的相互作用。在 HL-60 细胞中，ATO 与 5-Aza-2'-脱氧胞苷（DAC）之间存在协同作用，而在 U937 细胞中，ATO 与丙戊酸（VPA）之间存在拮抗作用。ATO 与曲古抑菌素 A（TSA）联合在 U937 和 K562 细胞中引起拮抗作用。这些结果不仅突出了 ATO 抗白血病机制的多样性，而且为进一步研究基于 ATO 与表观遗传药物联合的白血病治疗提供了初步指导。
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