中国药房2026，Vol.37Issue(1)：36-41,6.DOI:10.6039/j.issn.1001-0408.2026.01.07
秦皮乙素调控AKT/SKP2/MTH1通路诱导急性髓系白血病HL-60细胞凋亡的作用研究
Study on the apoptosis-inducing effect of esculetin on acute myeloid leukemia HL-60 cells via regulating the AKT/SKP2/MTH1 pathway
摘要
Abstract
OBJECTIVE To investigate the apoptosis-inducing effect of esculetin(Esc)on acute myeloid leukemia(AML)HL-60 cells by regulating the protein kinase B(AKT)/S-phase kinase-associated protein 2(SKP2)/MutT homolog 1(MTH1)pathway.METHODS AML HL-60 cells were randomly divided into control group(routine culture),Esc low-concentration group(L-Esc group,25 μmol/L Esc),Esc medium-concentration group(M-Esc group,50 μmol/L Esc),Esc high-concentration group(H-Esc group,100 μmol/L Esc),and high-concentration of Esc+SC79(AKT agonist)group(100 μmol/L Esc+5 μmol/L SC79).Cell proliferation in each group was detected by MTT assay and colony formation assay.The level of reactive oxygen species(ROS)in cells was measured by using the CM-H2 DCFDA fluorescent probe.Cell apoptosis was analyzed by flow cytometry.Western blot assay was performed to detect the expression levels of apoptosis-related proteins[B-cell lymphoma 2(Bcl-2),Bcl-2-associated X protein(Bax),cleaved caspase-3],AKT/SKP2/MTH1 pathway-related proteins(p-AKT,AKT,SKP2,MTH1),along with the upstream and downstream proteins of AKT phosphatidylinositol 3-kinase(PI3K),cyclin-dependent kinase inhibitor 1(P21)and cyclin-dependent kinase inhibitor 1B(P27).RESULTS Compared with control group,the cell viability,colony number,and the phosphorylation levels of AKT and PI3K proteins as well as protein expressions of SKP2,MTH1 and Bcl-2 were significantly decreased(P＜0.05),while ROS level,apoptosis rate,and the expression levels of Bax,cleaved caspase-3,P21 and P27 proteins were significantly increased(P＜0.05).Moreover,the effects of Esc exhibited concentration-dependence(P＜0.05).Compared with H-Esc group,above indexes of high-concentration of Esc+SC79 group were reversed significantly(P＜0.05).CONCLUSIONS Esc may promote massive ROS production and induce activation of apoptosis in HL-60 cells by inhibiting the AKT/SKP2/MTH1 pathway,thus inhibiting the proliferation of HL-60 cells.关键词
秦皮乙素/急性髓系白血病/HL-60细胞/蛋白激酶B/细胞凋亡/AKT/SKP2/MTH1通路Key words
esculetin/acute myeloid leukemia/HL-60 cells/protein kinase B/cell apoptosis/AKT/SKP2/MTH1 pathway分类
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宋卫华,褚福营,谢玮,陈金亮,赵枰,仇宏,陶健,陈相..秦皮乙素调控AKT/SKP2/MTH1通路诱导急性髓系白血病HL-60细胞凋亡的作用研究[J].中国药房,2026,37(1):36-41,6.基金项目
江苏省基础研究计划(自然科学基金)面上项目(No.BK20191207) （自然科学基金）
南通市科技项目(No.MS22021001) （No.MS22021001）
