黄芪甲苷调控DDR1/PI3K/Akt信号通路对急性髓系白血病HL-60细胞增殖、凋亡的影响  

Effect of astragalosideⅣmodulation of DDR1/PI3K/Akt signaling pathway on proliferation and apoptosis of HL-60 cells in acute myeloid leukemia

作　　者：任晓艳 方芳 于玲 王萍 REN Xiao-yan;FANG fang;YU Ling;WANG Ping(Dept of Hematology of Zhumadian Central Hospital,Zhumadian Henan 463000,China;College of Pharmacy,Nanjing Medical University,Nanjing 210029,China;Dept of Oncology,First Affiliated Hospital of Sun Yat-sen University,Guangzhou 510080,China)

机构地区：[1]驻马店市中心医院血液内科,河南驻马店463000 [2]南京医科大学药学院,江苏南京210029 [3]中山大学附属第一医院肿瘤科,广东广州510080

出　　处：《中国药理学通报》2025年第5期935-941,共7页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金青年科学基金项目(No 82104962);河南省中医药科学研究专项课题(No 2019ZY1018)。

摘　　要：目的探讨黄芪甲苷(astragaloside IV,AS-Ⅳ)对急性髓系白血病HL-60细胞增殖、凋亡以及盘状结构域受体1(discoid domain receptor 1,DDR1)/磷脂酰肌醇3-激酶/蛋白激酶B(phosphatidylinositol 3-kinase/protein kinase B,PI3K/Akt)信号通路的影响。方法实验分为对照组(Control)、AS-Ⅳ干预组、Control+DDR1基因干扰组(sh-DDR1)、AS-Ⅳ+DDR1基因过表达组(AS-Ⅳ+OVE-DDR1)及AS-Ⅳ+OVE-DDR1+PI3K抑制剂组(AS-Ⅳ+OVE-DDR1+LY294002)。AS-Ⅳ干预72 h后,CCK-8法测定细胞增殖抑制率;流式细胞术和Hoechst33258染色法检测细胞凋亡;Western blot检测DDR1/PI3K/Akt信号通路蛋白,增殖及凋亡相关蛋白表达水平。结果与Control组相比,AS-Ⅳ组细胞增殖率明显降低,凋亡率明显升高(P<0.01),细胞呈现核固缩、核碎裂等细胞凋亡形态变化,DDR1、p-PI3K、p-Akt、细胞周期素D1(CyclinD1)、Bcl-2蛋白表达明显降低,caspase-3蛋白表达均明显升高(P<0.01)。与AS-Ⅳ组相比,AS-Ⅳ+OVE-DDR1组细胞增殖率明显升高,凋亡率明显降低(P<0.01),DDR1、p-PI3K、p-Akt、CyclinD1、caspase-3蛋白表达均明显升高,Bcl-2蛋白表达明显降低(P<0.01)。与AS-Ⅳ+OVE-DDR1组相比,AS-Ⅳ+OVE-DDR1+LY294002组细胞增殖率明显降低,凋亡率明显升高(P<0.01),DDR1、p-PI3K、p-Akt、CyclinD1、caspase-3蛋白表达均明显降低,Bcl-2蛋白表达明显升高(P<0.01)。结论AS-Ⅳ能够抑制急性髓系白血病HL-60细胞增殖,促进细胞凋亡,其机制与抑制DDR1/PI3K/Akt信号通路相关。Aim To investigate the effects of astragalosideⅣ(AS-Ⅳ)on proliferation,apoptosis and the discoid domain receptor 1/phosphatidylinositol 3-kinase/protein kinase B(DDR1/PI3K/Akt)signaling pathway of HL-60 cells in acute myeloid leukemia.Methods The experiment was divided into the control group(Control),AS-Ⅳintervention group,control+DDR1 gene interference group(Control+sh-DDR1),AS-Ⅳ+DDR1 gene overexpression group(AS-Ⅳ+OVE-DDR1)and AS-Ⅳ+OVE-DDR1+PI3K inhibitor group(AS-Ⅳ+OVE-DDR1+LY294002).After 72 h of AS-Ⅳintervention,the proliferation inhibition rate was measured by CCK-8;apoptosis was detected by flow cytometry and Hoechst33258 staining;and the expression levels of DDR1/PI3K/Akt signaling pathway proteins,proliferation and apoptosis-related proteins were detected by Western blot.Results Compared with the Control group,the AS-Ⅳgroup showed significantly lower proliferation rate and higher apoptosis rate(P<0.01),cells showed apoptotic morphological changes such as nuclear sequestration and nuclear fragmentation,and the expression of DDR1,p-PI3K,p-Akt,CyclinD1 and Bcl-2 proteins were significantly lower and caspase-3 protein expression was significantly higher(P<0.01).Compared with the AS-Ⅳgroup,cell proliferation rate was significantly higher and apoptosis rate was significantly lower in the AS-Ⅳ+OVE-DDR1 group(P<0.01),and DDR1,p-PI3K,p-Akt,CyclinD1,and caspase-3 protein expression were significantly higher and Bcl-2 protein expression was significantly lower in the AS-Ⅳ+OVE-DDR1 group(P<0.01).Compared with the AS-Ⅳ+OVE-DDR1 group,the cell proliferation rate was significantly lower and apoptosis rate was significantly higher in the AS-Ⅳ+OVE-DDR1+LY294002 group(P<0.01),and DDR1,p-PI3K,p-Akt,CyclinD1,and caspase-3 protein expression were significantly lower and Bcl-2 protein expression was significantly higher in the AS-Ⅳ+OVE-DDR1+LY294002 group(P<0.01).Conclusion AS-Ⅳcan inhibit proliferation and promote apoptosis in acute myeloid leukemia HL-60 cells by a mechanism related to the in

关 键 词：急性髓系白血病 黄芪甲苷 盘状结构域受体1/磷脂酰肌醇3-激酶/蛋白激酶B通路 增殖 凋亡 

分 类 号：R284.1[医药卫生—中药学] R329.25[医药卫生—中医学] R329.28R345.57R392.11R733.71