TAK-733，一种选择性MEK抑制剂，增强了伏洛昔明诱导的髓系白血病细胞凋亡。
TAK-733, a Selective MEK Inhibitor, Enhances Voreloxin-induced Apoptosis in Myeloid Leukemia Cells.
作者信息
Jasek-Gajda Ewa, Gajda Mariusz, Jasińska Małgorzata, Litwin Jan A, Lis Grzegorz J
机构信息
Department of Histology, Jagiellonian University Medical College, Krakow, Poland
Department of Histology, Jagiellonian University Medical College, Krakow, Poland.
出版信息
Anticancer Res. 2018 Nov;38(11):6147-6156. doi: 10.21873/anticanres.12967.
BACKGROUND/AIM: MEK inhibitors are new promising anticancer drugs. The aim of this study was to investigate the effect of the combination treatment of voreloxin with the MEK inhibitor TAK-733 on HL60 myeloid leukemia cells.
MATERIALS AND METHODS
MAPK activity, cell viability, apoptosis, oxidative stress induction and AIF (apoptosis-inducing factor) distribution were assessed in HL60 cells cultured with each drug alone or with both drugs.
RESULTS
TAK-733 alone at 5 μM significantly reduced MAPK activity and did not influence viability and apoptosis in HL60 cells. Voreloxin at concentration of 0.03-0.48 μM reduced cell viability and increased apoptosis rate. Incubation with both drugs caused further inhibition of cell viability and increased apoptosis associated with generation of reactive oxygen species (ROS) and nuclear translocation of AIF.
CONCLUSION
Combination of TAK-733 and voreloxin can exert a synergistic anticancer effect in myeloid leukemia cells.
背景/目的：MEK抑制剂是新型且有前景的抗癌药物。本研究旨在探究沃洛昔星与MEK抑制剂TAK-733联合治疗对HL60髓系白血病细胞的影响。
材料与方法
评估单独使用每种药物或两种药物联合培养的HL60细胞中的MAPK活性、细胞活力、凋亡、氧化应激诱导及凋亡诱导因子（AIF）分布情况。
结果
5 μM的TAK-733单独使用可显著降低MAPK活性，且不影响HL60细胞的活力和凋亡。浓度为0.03 - 0.48 μM的沃洛昔星可降低细胞活力并提高凋亡率。两种药物共同孵育导致细胞活力进一步受到抑制，并增加与活性氧（ROS）生成及AIF核转位相关的凋亡。
结论
TAK-733与沃洛昔星联合可在髓系白血病细胞中发挥协同抗癌作用。
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