莪术醇通过PI3K/AKT信号通路介导急性髓系白血病细胞程序性死亡  

Curcumol Mediates the Programmed Cell Deathin Acute Myeloid Leukemiathrough PI3K/AKT Signaling Pathway

作　　者：李祚涛 陈小芸 李海亮 冷桂香 刘彦权 郭灵 王钇力 LI Zuo-Tao;CHEN Xiao-Yun;LI Hai-Liang;LENG Gui-Xiang;LIU Yan-Quan;GUO Ling;WANG Yi-Li(Department of Intensive Medicine,The First Affiliated Hospital of Gannan Medical University,Ganzhou 341000,Jiangxi Province,China;Department of Hematology,The First Affiliated Hospital of Gannan Medical University,Ganzhou 341000,Jiangxi Province,China;Department of Medical Imaging,The First Affiliated Hospital of Gannan Medical University,Ganzhou 341000,Jiangxi Province,China;Department of Hematology,The First Dongguan Affiliated Hospital of Guangdong Medical University,Dongguan 523808,Guangdong Province,China;Department of Oncology,The First Affiliated Hospital of Gannan Medical University,Ganzhou 341000,Jiangxi Province,China)

机构地区：[1]赣南医科大学第一附属医院重症医学科,江西赣州341000 [2]赣南医科大学第一附属医院血液内科,江西赣州341000 [3]赣南医科大学第一附属医院医学影像科,江西赣州341000 [4]广东医科大学附属东莞第一医院血液内科,广东东莞523808 [5]赣南医科大学第一附属医院肿瘤内科,江西赣州341000

出　　处：《中国实验血液学杂志》2024年第6期1682-1688,共7页Journal of Experimental Hematology

基　　金：国家自然科学基金(62161001);江西省中医药管理局科技计划项目(2022B072)。

摘　　要：目的:探讨莪术醇对急性髓系白血病(AML)细胞恶性生物学特性的影响及其分子机制,为传统中医药抗白血病治疗提供理论与实验依据。方法:用不同浓度莪术醇作用于AML细胞株HL-60、KG-1细胞后,CCK-8法检测细胞增殖活力,Western blot检测凋亡蛋白和PI3K/AKT信号通路蛋白的表达变化,实时荧光定量聚合酶链式反应(RT-qPCR)检测Caspase家族mRNA的表达情况。结果:莪术醇可抑制HL-60、KG-1细胞的增殖活性,并诱导细胞凋亡,其通过上调Bax蛋白表达并下调Bcl-2蛋白的表达以促进细胞凋亡(P<0.05)。当莪术醇干预HL-60、KG-1细胞后,其亦可通过抑制PI3K/AKT信号通路激活而诱导AML细胞的程序性死亡。此外,莪术醇干预后可上调HL-60细胞的Caspase 3、Caspase 6、Caspase 8以及Caspase 9的表达(P<0.05),可显著上调KG-1细胞的Caspase 3、Caspase 8和Caspase 9的表达(P<0.01),对Caspase 6的表达影响微弱(P<0.05),但低浓度(<60μg/ml)莪术醇对KG-1细胞Caspase 6的表达基本无影响(P>0.05)。结论:莪术醇可能通过抑制PI3K/AKT信号通路的激活、影响Bcl-2家族蛋白表达以及促进Caspase家族核心成员活化等介导AML细胞程序性死亡,从而发挥抗白血病作用。Objective:To investigate the effects of Curcumol on the malignant biological characteristics of acute myeloid leukemia(AML)cells and its molecular mechanism,and to provide theoretical and experimental evidence for the anti-leukemia treatment of traditional Chinese medicine.Methods:After the AML cell lines HL-60 and KG-1 cells were treated different concentrations of with Curcumol.The proliferation activity of cells was detected by CCK-8 method,and the expression changes of apoptotic proteins and PI3K/AKT signaling pathway proteins were detected by Western blot.Real-time quantitative fluorescence polymerase chain reaction(RT-qPCR)was used to detect the expression of Caspase family mRNA.Results:Curcumol could inhibit the proliferation and induce apoptosis of HL-60 and KG-1 cells,promote apoptosis by up-regulating the expression of Bax and down-regulating the expression of Bcl-2 protein(P<0.05).When Curcumol interferes with HL-60 and KG-1 cells,it can also induce programmed cell death of AML by inhibiting PI3K/AKT signaling pathway.In addition,after the intervention of Curcumol,the expression of Caspase 3,Caspase 6,Caspase 8 and Caspase 9 were up-regulated in HL-60 cells(P<0.05),the expression of Caspase 3,Caspase 8 and Caspase 9 were significantly up-regulated in KG-1 cells(P<0.01),while the expression of Caspase 6 was weakly affected(P<0.05),but low concentration of Curcumol(<60μg/ml)had no effect on the expression of Caspase 6 in KG-1 cells(P>0.05).Conclusion:Curcumol may mediate the programmed death of AML cells by inhibiting the PI3K/AKT signaling pathway,affecting the expression of Bcl-2 family proteins,and promoting the activation of core members of Caspase family,so as to play an anti-leukemia role.

关 键 词：莪术醇 急性髓系白血病 程序性死亡 抗癌机制 

分 类 号：R733.71[医药卫生—肿瘤] R285[医药卫生—临床医学]