百里香醌对急性髓系白血病细胞恶性增殖抑制作用的分子机制  

Molecular Mechanism of Thymoquinone Inhibition on Malignant Proliferation of Acute Myeloid Leukemia Cells

作　　者：林洁 曾繁林 刘彦权 严志民 李祚涛 许庆林 朱宏泉 LIN Jie;ZENG Fan-Lin;LIU Yan-Quan;YAN Zhi-Min;LI Zuo-Tao;XU Qing-Lin;ZHU Hong-Quan(Department of Intensive Medicine,The First Affiliated Hospital of Gannan Medical University,Ganzhou 341000,Jiangxi Province,China;Department of Hepatobiliary Surgery,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 Hematology,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肝胆外科,江西赣州341000 [3]广东医科大学附属东莞第一医院血液内科,广东东莞523808 [4]赣南医科大学第一附属医院血液内科,江西赣州341000

出　　处：《中国实验血液学杂志》2025年第2期311-318,共8页Journal of Experimental Hematology

基　　金：江西省教育厅科学技术研究立项课题(GJJ211530,GJJ2201414);江西省中医药管理局科技计划项目(2022B072)。

摘　　要：目的:探讨百里香醌对急性髓系白血病细胞增殖的影响及其分子机制,为祖国传统中医药抗白血病基础研究提供理论依据。方法:不同浓度梯度百里香醌干预HL-60、THP-1细胞,CCK-8法检测细胞增殖,Wright-Giemsa法检测细胞形态学改变,Annexin V/PI双染流式细胞术检测细胞凋亡,Western blot检测凋亡及信号通路蛋白表达情况,实时荧光定量PCR技术和Western blot检测SRY相关高迁移率族蛋白(SOX)家族成员的表达变化。结果:百里香醌可抑制HL-60、THP-1细胞恶性增殖,并上调促凋亡蛋白Bax表达,下调抗凋亡蛋白Bcl-2以及凋亡抑制因子Survivin的表达,同时水解活化Caspase-3继而诱导HL-60、THP-1细胞发生凋亡。百里香醌均可显著下调PI3K、Akt和m TOR的磷酸化水平,通过抑制PI3K/Akt/mTOR通路激活来遏制HL-60、THP-1细胞恶性生物学特性。百里香醌干预HL-60、THP-1细胞后,可显著下调SOX2、SOX4的表达,低浓度(<10μmol/L)百里香醌对SOX12表达的影响微弱,随着浓度升高可下调SOX12的表达,但对SOX11表达基本无影响。结论:百里香醌可遏制AML细胞增殖,其机制可能与抑制PI3K/Akt/mTOR信号通路激活、调控凋亡蛋白和SOX家族核心成员表达水平有关。Objective:To investigate the effects of thymoquinone on the proliferation of acute myeloid leukemia(AML)cells and its molecular mechanism,so as to provide theoretical basis for the basic research on the anti-leukemia of traditional Chinese medicine.Methods:The HL-60 and THP-1 cells were treated with thymoquinone at different concentration gradients,cell proliferation was detected by CCK-8 method,morphological changes were detected by Wright-Giemsa method,apoptosis was detected by Annexin V/PI double staining flow cytometry,and apoptosis and signal pathway protein expression were detected by Western blot.Real-time quantitative fluorescence PCR and Western blot were used to detect the expression changes of high mobility family members of SRY-related proteins(SOX).Results:Thymoquinone inhibited the malignant proliferation of HL-60 and THP-1 cells,up-regulated the expression of pro-apoptotic protein Bax,down-regulated the expression of anti-apoptotic protein Bcl-2 and Survivin,and hydrolyzed Caspase-3 to induce the apoptosis of HL-60 and THP-1 cells.Thymoquinone could also significantly down-regulate the phosphorylation of PI3K,Akt and mTOR,and inhibit the malignant biological characteristics of HL-60 and THP-1 cells by inhibiting the activation of PI3K/Akt/mTOR pathway.After thymoquinone intervention in HL-60 and THP-1 cells,the expression of SOX2 and SOX4 could be down-regulated significantly.At low concentration(<10μmol/L),the expression of SOX12 was weakly affected by thymoquinone.With increasing concentration,the expression of SOX12 could be down-regulated,however,thymoquinone had no effect on SOX11 expression.Conclusion:Thymoquinone can inhibit the proliferation of AML cells,and its mechanism may be related to inhibiting the activation of PI3K/Akt/mTOR signaling pathway,regulating the expression of apoptotic proteins and core members of SOX family.

关 键 词：百里香醌 急性髓系白血病 恶性增殖 抗癌作用 分子机制 

分 类 号：R733.71[医药卫生—肿瘤]