胆木抗肝癌活性的网络药理学及初步细胞筛选研究  

Network pharmacology and preliminary cell screening studies on the anti⁃liver cancer activity of Nauclea Officinalis

作　　者：陈维佳 周明艳 胡继成 祝哲 徐剑 CHEN Wei-jia;ZHOU Ming-yan;HU Ji-cheng;ZHU Ze;XU Jian(Department of Organ Transplantation,the Second Affiliated Hospital of Hainan Medical University,Haikou 570105,China;Institute of Clinical Medicine,the Second Affiliated Hospital of Hainan Medical University,Haikou 570105,China;Hainan Institute of Organ Transplantation,Haikou 570105,China)

机构地区：[1]海南医学院第二附属医院器官移植科,海南海口570105 [2]海南医学院第二附属医院临床医学研究所,海南海口570105 [3]海南省器官移植研究所,海南海口570105

出　　处：《海南医学院学报》2023年第12期881-889,898,共10页Journal of Hainan Medical University

基　　金：海南省重大科技计划项目(ZDKJ2019009);海南省临床医学中心建设项目。

摘　　要：目的:基于网络药理学探究胆木抗肝癌的作用机制,并通过细胞筛选初步验证胆木抗肝癌活性。方法:利用网络药理学筛选胆木与肝癌的共同靶点,构建蛋白互作网络以及进行富集分析及作用机制预测,并将胆木的主要活性成分与核心靶点进行分子对接。利用CCK8、细胞凋亡及PCR等体外细胞实验进行初步验证。结果:经筛选获得胆木活性成分14种,相关的靶点587个,与肝癌靶点映射后共同靶点有288个,主要有TP53、SRC、STAT3等核心靶点。其中异长春花苷内酰胺、短小蛇根草苷、喜果苷等化合物可能是胆木抗肝癌的潜在活性成分,可能通过介导癌症通路、PI3K/Akt和EGFR酪氨酸激酶抑制剂抵抗等信号通路,参与蛋白质磷酸化、凋亡过程的负调控等过程,发挥抗肝癌作用;分子对接结果显示胆木活性成分与肝癌核心靶点产生稳定的结合;体外细胞实验结果表明,胆木中主要成分异长春花苷内酰胺对肝癌细胞具有细胞毒性,抑制肝癌细胞增殖(P<0.001),内在机制是下调肝癌HepG2细胞SRC、STAT3、MAPK3的基因表达(P<0.05),并诱导肝癌细胞凋亡(P<0.001)。结论:本研究初步探讨了胆木活性成分抗肝癌的潜在机制及初步药效作用,为胆木抗肝癌作用机制研究提供理论依据。Objective:To explore the mechanism of Nauclea Officinalis of anti-liver cancer effect based on network phar-macology,and to preliminarily verify anti-liver cancer activity of Nauclea Officinalis through cell screening.Methods:Network pharmacology was used to screen for common targets of Nauclea Officinalis and liver cancer,protein-protein interaction(PPI)net-work was constructed,and enrichment analysis and mechanism prediction were conductd.Molecular docking of main active ingre-dients of Nauclea Officinalis with core targets was made.Preliminary verification was performed by in vitro cell experiments such as CCK8,cell apoptosis,and PCR.Results:After the screening,14 active ingredients of Nauclea Officinalis were obtained,with 587 related targets.After mapping with liver cancer targets,there were 288 common targets,mainly including TP53,SRC,STAT3,and other core targets.Among them,compounds such as strictosamide,pumiloside and vincosamide may be potential active ingredients of Nauclea Officinalis of anti-liver cancer effect.They may participate in protein phosphorylation and negative regulation of the apoptosis process by mediating cancer pathways,PI3K/Akt and EGFR tyrosine kinase inhibitors resistance sig-naling pathways to play an anti-liver cancer role;molecular docking results showd that active ingredients of Nauclea Officinalis had a stable binding with liver cancer core targets;in vitro cell experiments showd that main ingredient strictosamide of Nauclea Officinalis had cytotoxicity against liver cancer cells,inhibited liver cancer cell proliferation(P<0.001),down-regulated gene ex-pression of liver cancer HepG2 cells SRC,STAT3,MAPK3(P<0.05),and induced liver cancer cell apoptosis(P<0.001).Conclusion:This study preliminarily explores the potential mechanism of active ingredients of Nauclea Officinalis against liver cancer and its preliminary pharmacological effects,providing a theoretical basis for the study of Nauclea Officinalis of anti-liver cancer mechanism.

关 键 词：胆木 肝癌 网络药理学 作用机制 体外细胞实验 

分 类 号：R285[医药卫生—中药学]