内科理论与实践2017,Vol.12Issue(4):293-297,5.DOI:10.16138/j.1673-6087.2017.04.013
高三尖杉酯碱联合尼洛替尼治疗M2b型急性髓系白血病
Treatment of acute myeloid leukemia M2b with homoharringtonine in combination with nilotinib
摘要
Abstract
Objective To investigate the effect of combined homoharringtonine (HHT) and nilotinib on M2b subtype of acute myeloid leukemia(AML-M2b).Methods Cell counting kit-8(CCK-8) assay was used to detect the cell viability and evaluate the drug toxicity on AML-M2b cell line Kasumi-1.Expressions of stem cell factor receptor(C-KIT) and apoptosis re lated proteins were determined by Western blotting.Combined drug effect index (CI) was calculated using CompuSyn software.Mice model transplanted with leukemic cells bearing AML1-ETO fusion gene and C-KIT mutation was used to evaluate the in vivo effect of HHT and nilotinib.Flow cytometry was used to detect the green fluorescent protein (GFP) positive leukemic cells in mice.The survival of mice was measured by using Graphpad Prism software.Results A dose-dependent growth inhibition was observed following the treatment with HHT or nilotinib in Kasumi-1 cells (r=0.933,P=0.007,r=0.897,P=0.03),and the combination of these two drugs produced a synergistic effect (CI<0.9).In vivo,HHT combined with nilotinib could significantly inhibit the proliferation of leukemic cells and synergistically prolong the lifespan of leukemic mice when compared with HHT or nilotinib alone (P=0.001 4 and P=0.047 5).Conclusions HHT combined with nilotinib could exert synergistic effect on AML-M2b leukemic cells,thus providing a potential therapeutic regimen for AML-M2b.关键词
M2b型急性髓系白血病/高三尖杉酯碱/尼洛替尼/Kasumi-1细胞株/协同作用Key words
Acute myeloid leukemia M2b subtype/Homoharringtonine/Nilotinib/Kasumi-1 cell line/Synergistic effect分类
医药卫生引用本文复制引用
夏莉,张伟娜,王月英..高三尖杉酯碱联合尼洛替尼治疗M2b型急性髓系白血病[J].内科理论与实践,2017,12(4):293-297,5.基金项目
上海市教育委员会高峰高原学科建设计划(项目编号:20152507) (项目编号:20152507)
2014年度上海交通大学“SMC-晨星青年学者计划” ()
上海交通大学医学院博士创新基金项目(项目编号:2014282) (项目编号:2014282)