新型含氮双氢青蒿素二聚体对人白血病细胞株NB4-R1细胞凋亡的影响  

Effect of a Novel Dihydroartemisinin Dimer Containing Nitrogen Atoms SM 1044 on Apoptosis of Human Leukemia Cell Line NB4-R1

作　　者：崔雯 薛征[1] 赵玲玲[2] 李英[4] 糜坚青 CUI Wen;XUE Zheng;ZHAO Ling-Ling;LI Ying;MI Jian-Qing(Department of Pediatrics,Shanghai Municipal Hospital of Traditional Chinese Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 200071,China;Department of Hematology,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai Institute of Hematology,Shanghai 200025,China;Department of Clinical Laboratory,Shanghai Municipal Hospital of Traditional Chinese Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 200071,China;Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China)

机构地区：[1]上海中医药大学附属市中医医院儿科,上海200071 [2]上海交通大学医学院附属瑞金医院血液科,上海血液学研究所,上海200023 [3]上海中医药大学附属市中医医院检验科,上海200071 [4]中国科学院上海药物研究所,上海201203

出　　处：《中国实验血液学杂志》2023年第3期659-665,共7页Journal of Experimental Hematology

基　　金：上海市青年科技英才扬帆计划(20YF1446000);国家自然科学基金(81670147)。

摘　　要：目的:探讨新型水溶性含氮双氢青蒿素二聚体SM 1044对全反式维甲酸耐药急性早幼粒细胞白血病细胞株NB4-R1细胞凋亡的影响及其可能的机制。方法:流式细胞术检测SM 1044对细胞凋亡、线粒体跨膜电位以及细胞活性氧(ROS)水平的影响,Western blot检测SM 1044对MAPK(ERK、JNK)信号通路以及PML/RARα融合蛋白的影响和凋亡相关蛋白表达的变化。结果:SM 1044能够显著诱导NB4-R1细胞发生细胞凋亡以及线粒体跨膜电位丢失,同时能活化凋亡相关蛋白caspase-3、caspase-8、caspase-9以及抗多腺苷二磷酸核糖聚合酶;SM 1044可诱导NB4-R1细胞产生ROS;Western blot检测结果显示,SM 1044能够激活MAPK(ERK、JNK)信号通路的磷酸化,同时下调PML/RARα融合蛋白的表达。结论:SM 1044能够诱导全反式维甲酸耐药急性早幼粒细胞白血病细胞株NB4-R1细胞凋亡,其诱导凋亡可能与ROS/ERK以及ROS/JNK信号通路有关,此外,SM 1044也可通过下调PML/RARα融合蛋白诱导细胞凋亡。Objective:To investigate the effect of a water-soluble novel dihydroartemisinin dimer containing nitrogen atoms SM 1044 on the apoptosis of all-trans retinoic acid (ATRA) resistant acute promyelocytic leukemia (APL) NB4-R1cells and its potential mechanism.Methods:The effects of SM 1044 on cell apoptosis,mitochondrial transmembrane potential,and the level of reactive oxygen species (ROS) were assessed by flow cytometry.Expressions of apoptosisrelated proteins were determined by Western blot.The effects of SM 1044 on MAPK (ERK,JNK) signaling pathway,PML/RARα fusion protein,and expressions of apoptosis-related proteins were detected by Western blot.Results:SM1044 could significantly induce apoptosis and the loss of mitochondrial transmembrane potential in NB4-R1 cells,and activate apoptosis-related proteins caspase-3,caspase-8,caspase-9 and poly (ADP-ribose) polymerase (PARP).SM 1044could also induce NB4-R1 cells to produce ROS.Western blot showed that SM 1044 activated the phosphorylation of MAPK (ERK,JNK) signaling pathway and down-regulated the expression of PML/RARα fusion protein.Conclusion:SM 1044 can induce apoptosis of ATRA resistant APL NB4-R1 cells,which may be related to ROS/ERK and ROS/JNK signaling pathway,and can also induce by down-regulating PML/RARα fusion protein.

关 键 词：青蒿素衍生物 急性早幼粒细胞白血病 NB4-R1细胞 细胞凋亡 

分 类 号：R733.71[医药卫生—肿瘤]