三氧化二砷对急性早幼粒细胞白血病细胞株Hedgehog信号通路的影响  

Inhibition of arsenic trioxide on Hedgehog pathway in acute promyelocytic leukemia cell line

作　　者：杨东光[1] 曹峰林[1] 叶向梅[1] 赵辉[1] 李洋[1] 王洪玲[1] 周晋[1] 

机构地区：[1]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150525

出　　处：《江苏大学学报（医学版）》2013年第5期389-392,共4页Journal of Jiangsu University：Medicine Edition

基　　金：黑龙江省青年科学基金资助项目(QC2009C27)

摘　　要：目的:探讨三氧化二砷(As2O3)对急性早幼粒细胞白血病细胞Hedgehog信号转导通路相关分子的作用,为将其扩大应用于其他具有Hedgehog异常活化的肿瘤提供理论基础。方法:将不同浓度的As2O3作用于急性早幼粒细胞白血病NB4细胞株48 h,采用实时定量PCR(qRT-PCR)和免疫印迹技术检测Hedgehog信号转导通路关键分子Smoothened(Smo)、Ptch、Gli1和Gli2在mRNA和蛋白水平的变化。结果:As2O3处理后,NB4细胞的Smo、Ptch、Gli2在蛋白和mRNA水平均受到明显抑制,差异有统计学意义。结论:As2O3可能是通过抑制Gli2蛋白和mRNA发挥抗Hedgehog信号转导通路的作用,而Hedgehog信号转导通路可能是As2O3发挥抗急性早幼粒细胞白血病的机制之一。Objective： Human acute promyelocytic leukemia（APL） cell line NB4 was used as a model to discuss whether arsenic trioxide（ATO） can inhibit the expression of Hedgehog signaling pathway molecules,so that we can provide a theoretical basis for the application of ATO in other cancers with an aberrant activation of Hedgehog signaling pathway.Methods： Treated with ATO of different concentration,the expression of Hh pathway components such as Smo,Ptch,Gli1 and Gli2 were analyzed with real time quantitative reverse transcription polymerase chain reaction（qRT-PCR） and Western Blot in NB4 at mRNA and protein level.Results： After ATO treatment,the expression of Smo,Ptch and Gli2 were significantly downregulated in NB4.Conclusion： ATO may inhibit the expression of Hh signaling pathway through the mRNA and protein inhibition of the key Gli2 target transcription factor and ATO may inhibit APL partly through the inhibition of Hedgehog signaling pathway.

关 键 词：急性早幼粒细胞白血病 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：R733.71[医药卫生—肿瘤]