三氧化二砷对慢性粒细胞白血病Hedgehog信号转导通路分子蛋白表达的影响  

Effect of Arsenic Trioxide on Molecular Gene Expression of Hedgehog Signaling Pathway of Chronic Myelogenous Leukemia

作　　者：马咏歌 宋鹏[2] 叶向梅[2] 赵辉[2] 刘志宇[2] 张丽坤[2] 刚宏林[1,3] 杨东光 MA Yongge;SONG Peng;YE Xiangmei;ZHAO Hui;LIU Zhiyu;ZHANG Likun;GANG Honglin;YANG Dongguang(Heilongjiang University of Chinese Medicine,Harbin 150040,China;The First Affiliated Hospital of Harbin Medical University,Harbin 150001,China;Harbin Food and Drug Inspection Center,Harbin 150025,China)

机构地区：[1]黑龙江中医药大学,黑龙江哈尔滨150040 [2]哈尔滨医科大学附属第一医院中心血液实验室,黑龙江哈尔滨150001 [3]哈尔滨食品药品检验检测中心,黑龙江哈尔滨150025

出　　处：《中医药学报》2018年第3期39-42,共4页Acta Chinese Medicine and Pharmacology

基　　金：国家自然科学基金面上项目(81500117);黑龙江省自然科学基金青年基金项目(H2015058);黑龙江省博士后科研启动资金项目(LBH-Q14129)

摘　　要：目的:以人类慢性粒细胞白血病(CML)细胞株K562为模型,探讨三氧化二砷(ATO)是否对CML细胞具有诱导凋亡作用,并探讨ATO是否对Hedgehog(Hh)信号转导通路相关分子具有显著抑制作用。为将ATO应用于具有Hh异常活化的CML提供理论基础。方法:将不同浓度的ATO作用于K562细胞48 h,采用流式细胞术检测ATO对K562的诱导凋亡效果;采用免疫印迹(WB)技术检测ATO处理后Hh信号转导通路关键分子Gli2、Gli1、和Ptch2在蛋白水平的变化。结果:ATO处理后,K562细胞出现剂量依赖性凋亡效应,Ptch2和Gli2的蛋白均受到显著的影响,且差异有统计学意义。结论:在CML细胞中,ATO可能是以Gli2蛋白为靶点抑制Hh信号转导通路,该研究为扩大ATO应用于CML提供了理论基础。Objective： Cell line K562 of human chronic myelogenous leukemia（ CML） was used as the model to investigate whether arsenic trioxide（ ATO） can induce apoptosis of CML cells,and to explore whether ATO can inhibit the relative molecule expression of CML Hedgehog（ Hh） signal transduction pathway,so that providing the theoretical basis for applying ATO to CML with Hh activation. Methods： Different concentrations of ATO was applied in K562 cells for 48 hours,then flow cytometry was used to detect the apoptosis-inducing effect of ATO,and then Western blot（ WB） was used to detect the changes of Hh signal transduction molecule Gli2,Gli1,SMO and Ptch2 at protein levels. Results： After ATO intervention,K562 cells showed dose-dependent apoptosis effects,the protein expression of Gli2 and Ptch2 were significantly affected,and the difference was statistically significant. Conclusion： For CML cells,ATO may inhibit Hh signaling pathway by Gli2 protein target. This research provides a theoretical basis for expanding ATO application in CML.

关 键 词：慢性粒细胞白血病 三氧化二砷 Hedgehog信号转导通路 Gli1核转录因子 Gli2核转录因子 

分 类 号：R285[医药卫生—中药学] R733.72[医药卫生—中医学]