三氧化二砷对慢性粒细胞白血病Hedgehog信号转导通路分子基因表达影响的研究  

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

作　　者：田丽月 杨璐媛 吴龙月 张丽坤[2] 张鑫[2] 縢悦秋 刚宏林[1,3] 杨东光 TIAN Liyue;YANG Luyuan;WU Longyue;ZHANG Likun;ZHANG Xin;TENG Yueqiu;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：《中医药信息》2018年第4期9-13,共5页Information on Traditional Chinese Medicine

基　　金：国家自然科学基金面上项目(No.81500117);黑龙江省自然科学基金青年基金项目(No.H2015058);黑龙江省博士后科研启动资金项目(No.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)对CML的Hedgehog(Hh)信号转导通路相关分子的基因表达的作用,为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,免疫印迹(WB)技术检测ATO对CML致病关键分子P210/Bcr-Abl的影响,采用实时定量PCR(q RT-PCR)检测Hh信号转导通路关键分子Gli2、Gli1、SMO和Ptch在mRNA水平的变化。结果:ATO处理后,P210/Bcr-Abl蛋白表达呈剂量依赖性抑制(P<0.05),ATO对Gli1和Gli2 mRNA的表达具有显著的抑制作用,且抑制作用呈剂量依赖性(P<0.05)。ATO对ptch mRNA的表达具有上调作用(P<0.05)。但Smo mRNA的表达在各浓度ATO的作用下均未受到影响(P>0.05)。结论:在CML细胞中,ATO可通过抑制Gli1和Gli2 mRNA,上调Hh通路的抑制因子ptch mRNA的表达,并通过降解P210/Bcr-Abl蛋白发挥作用,且该研究为扩大ATO应用于CML提供了理论基础。Objective： Using human chronic myelogenous leukemia（ CML） cell line K562 as a model to investigate the effect of arsenic trioxide（ ATO） on the gene expression of CML Hedgehog（ Hh） signal transduction pathway molecule,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 Western blot（ WB）technique was used to detect the effect of ATO molecular pathogenic key protein P210/Bcr-Abl of CML,and then quantitative real-time PCR（ q RT-PCR） was used to detect the changes of Hh signal transduction molecule Gli2, Gli1, SMO and Ptch at mRNA levels. Results： After ATO treatment, the expression of P210/Bcr-Abl protein was inhibited in a dose-dependent manner（ P〈0. 05）. ATO could significantly inhibit the mRNA expression of Gli2 and Gli1 in a dose-dependent manner（ P〈0. 05）. ATO could also up-regulate the mRNA expression of ptch（ P〈0. 05）. However,the mRNA expression of Smo was not significantly inhibited（ P〉0. 05） in all concentrations of ATO. Conclusion： ATO may kill CML cells by inhibiting the mRNA expression of Gli2 and Gli1,and by up-regulating the mRNA expression of ptch and degradating the expression of P210/Bcr-Abl protein. This research provides a theoretical basis for ATO application in CML.

关 键 词：慢性粒细胞白血病 三氧化二砷 Hh信号转导通路 

分 类 号：R285.5[医药卫生—中药学]