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高三尖杉酯碱联合JQ1对急性髓系白血病细胞株Kasumi-1、Mv4-11的凋亡诱导作用
乐静, 李枫林, 牧启田, 袁娇娇, 裴仁治, 金洁, 陆滢
宁波市医疗中心李惠利东部医院血液肿瘤科
摘要:
目的探讨高三尖杉酯碱(HHT)联合BRD4抑制剂JQ1对急性髓系白血病(AML)细胞株Kasumi-1、Mv4-11的凋亡诱导作用。方法MTS法测HHT、JQ1单药及两药联合对AML细胞株的抑制作用,流式细胞仪检测两药联合对AML细胞株凋亡的作用,Westernblot法检测两药联合对凋亡相关蛋白(Bcl-2、Caspase-3、Parp)的作用。结果与HHT、JQ1单药比较,两药联合的抗白血病效应明显增强,能明显抑制AML细胞株Kasumi-1、Mv4-11的增殖;可促进细胞凋亡作用,并明显抑制Bcl-2蛋白表达,激活Caspase-3,促进Parp的裂解。结论HHT联合JQ1可以增强抗AML细胞株的作用,促进AML细胞株的凋亡,是有效的联合方案。
关键词:  白血病 高三尖杉酯碱 JQ1 凋亡
DOI:10.12056/j.issn.1006-2785.2018.40.10.2018-743
分类号:
基金项目:宁波市自然科学基金项目(2014A610232)
Homoharringtonine combined with BRD4 inhibitor JQ1 induces apoptosis of acute myeloid leukemia cells
Ningbo Medical Treatment Center Lihuili Hospital
Abstract:
Objective To investigate the effect of homoharringtonine (HHT) combined with BRD4 inhibitor JQ1 on apoptosis of acute myeloid leukemia (AML) cells. Methods AML Kasumi-1 and Mv4-11 cells were treated with HTT, JQ1 and HTT plus JQ1 in vitro, respectively. Cell proliferation was measured by MTS, and cell apoptosis was examined by flow cytometry. The expression of apoptosis-related proteins Bcl-2, Caspase-3 and Parp was detected by Western blot. Results Compared with JQ1 and HHT alone, the combination of the two drugs significantly increased the inhibition effect on the proliferation of Kasumi-1 and Mv4-11 cells. The combination of two drugs also significantly enhanced the effect on cell apoptosis, and enhanced the inhibition on the Bcl-2 expression, and the activation on caspase3 expression and Parp cleavage. Conclusion HHT combined with BRD4 inhibitor JQ1 can enhance the effect of two drugs against AML cells, inducing cell apoptosis.
Key words:  Leukemia HHT JQ1 Apoptosis