苦木碱B的抗肿瘤活性及其作用靶点  

Study on antitumor activity and its targets of 1-methoxycarbonyl-β-carboline

作　　者：李德平 刘文武 虞林玉 杨人泽 LI Deping;LIU Wenwu;YU Linyu;YANG Renze(Department of Pharmacy,The First Affiliated Hospital of Gannan Medical University,Ganzhou 341000,Jiangri,China;School of Pharmacy,Tsinghua University,Beijing 110084,China)

机构地区：[1]赣南医科大学第一附属医院药学部,江西赣州341000 [2]清华大学药学院,北京110084

出　　处：《西部医学》2025年第2期180-183,190,共5页Medical Journal of West China

基　　金：江西省中医药管理局科技计划项目(2023B1380);赣州市科技计划项目(GZ2023ZSF122)。

摘　　要：目的 探讨苦木碱B的抗肿瘤活性,并对其作用靶点进行分析,初步阐明其作用机制。方法 采用MTT法检测苦木碱B对多种肿瘤细胞活力的影响;采用ADP-Glo激酶检测法检测苦木碱B对217种激酶活力的影响;采用分子对接实验初步阐释苦木碱B与蛋白激酶混合连接激酶(MLK3)的作用方式。结果 苦木碱B对A549、HepG2、HCT11b、MCF-7等多种肿瘤细胞具有一定的抗肿瘤增殖活性;在10μM浓度下,苦木碱B对22种激酶的抑制率大于50%,其中,对MLK3的抑制率最高(88.41%);分子对接实验显示,苦木碱B能占据MLK3的ATP活性空腔,并与其铰链区的关键氨基酸残基ALA-196形成氢键作用。结论 苦木碱B可能通过抑制MLK3等靶点,从而发挥抗肿瘤的药理活性。Objective 1-methoxycarbonyl-β-carboline,an active ingredient exists in a number of Chinese herbs,has anti-tumor,anti-inflammation and other biological activities,but its target and mechanism are unclear.In this paper,the action target of 1-methoxycarbonyl-β-carboline was studied in order to elucidate its action mechanism.Methods MTT assay was used to detect the effects of 1-methoxycarbonyl-β-carboline on the viability of various tumor cells.ADP-Glo kinase assay was used to detect the effects of 1-methoxycarbonyl-β-carboline on 217 kinases.The interaction between 1-methoxycarbonyl-β-carboline and protein kinase MLK3 was elucidated by molecular docking experiment.Results 1-methoxycarbonyl-β-carboline had certain anti-tumor proliferation activity against various tumor cells.At the concentration of 10 μM,the inhibition rate of 1-methoxycarbonyl-β-carboline on 22 kinases was more than 50%.Among them,MLK3 showed the highest inhibition rate of(88.41%).Molecular docking experiments showed that 1-methoxycarbonyl-β-carboline could occupy the ATP-active cavity of MLK3 and form hydrogen bond with the key amino acid residue ALA-196 in its hinge region.Conclusion 1-methoxycarbonyl-β-carboline may exert anti-tumor pharmacological activity by inhibiting MLK3 and other kinase targets.

关 键 词：苦木碱B 抗肿瘤活性 作用靶点 混合连接激酶3 

分 类 号：R285.5[医药卫生—中药学]