基于网络药理学探讨粉防己碱抗肿瘤的潜在作用机制  

Analysis of the potential antitumor mechanism of Tetrandrine based on network pharmacology

作　　者：刘伟[1] 张彦忠[1] 白素平[2] 房立真[2] LIU Wei;ZHANG Yan-zhong;BAI Su-ping;FANG Li-zhen(Clinical Pharmacy Office,the Third Affiliated Hospital of Xinxiang Medical University,Xinxiang 453003,China;School of Pharmacy,Xinxiang Medical University,Xinxiang 453003,China)

机构地区：[1]新乡医学院第三附属医院临床药学办公室,河南新乡453003 [2]新乡医学院药学院,河南新乡453003

出　　处：《实用药物与临床》2020年第11期985-991,共7页Practical Pharmacy and Clinical Remedies

基　　金：国家自然科学基金资助面上项目(21672182)。

摘　　要：目的基于生物信息大数据分析,利用网络药理学分析方法,探讨粉防己碱多靶点、多通路抗肿瘤作用机制。方法借助于PharmMapper服务器、GeneCards数据库寻找粉防己碱抗肿瘤的潜在靶蛋白,建立潜在网络和蛋白质相互作用(PPI)网络,并通过Cytoscape进行可视化处理;运用Systems dock Web Site对核心靶点进行分子对接,验证网络分析结果;并借助KOBAS 3.0分析靶点基因生物功能及信号通路。结果数据分析结果表明,粉防己碱涉及的抗肿瘤作用靶点有86个,主要作用于雌激素受体1(ESR1)、一氧化氮合酶3(NOS3)、过氧化物酶体增殖物激活受体γ(PPARG)、血清白蛋白(ALB)、糖皮质激素受体(NR3C1)、E3泛素蛋白连接酶(MDM2)、酪氨酸蛋白激酶(LCK)、胰岛素样生长因子(IGF1)等靶蛋白基因,通路富集分析得到与其抗肿瘤作用有关的通路134条,主要涉及肿瘤通路、磷脂酰肌醇3-激酶/蛋白激酶B(PI3K-Akt)信号通路和代谢通路等信号通路。结论粉防己碱抗肿瘤作用具有多靶点、多通路特点,为后续开展其抗肿瘤作用机制研究提供了科学依据。Objective To discuss the multi-target and the multi-channel antitumor mechanism of action of Tetrandrine by adopting the analytical method of network pharmacology based on the big data analytics of biological information.Methods The potential target protein of tetrandrine with antitumor effect was searched for with the support of PharmMapper Server and GeneCards Database.The potential PPI net was founded and processed visually by Cytoscape.The system dock Web Site was used to perform molecular docking of core targets and verify network analysis results.The biological function and signal pathway of targeted gene was analyzed by KOBAS 3.0.Results According to the results of data analysis,there were 86 antitumor targets related to tetrandrine,whose mainly effect was on target protein genes such as ESR1,NOS3,PPARG,ALB,NR3C1,MDM2,LCK and IGF1.The enrichment of pathways showed that there were 134 pathways related to its antitumor effect,mainly involving pathways in tumor,PI3K-Akt signaling pathway,metabolic pathways and so on.Conclusion Tetrandrine has antitumor effect that is both multi-target and multichannel,which provides scientific basis for further research on its antitumor mechanism of action.

关 键 词：粉防己碱 网络药理学 抗肿瘤 分子对接 靶点 

分 类 号：R285[医药卫生—中药学]