基于网络药理学和分子对接探讨西黄丸治疗宫颈癌的作用机制  

Mechanism of Xihuang Pills in treatment of cervical cancer based on network pharmacology and molecular docking technology

作　　者：邓鸿飞 杨自力 罗毅[1] DENG Hongfei;YANG Zili;LUO Yi(Affiliated Hospital of Integrated Traditional Chinese and Western Medicine,Nanjing University of Traditional Chinese Medicine,Nanjing 210000,China)

机构地区：[1]南京中医药大学附属中西医结合医院,江苏南京210000

出　　处：《现代药物与临床》2024年第2期325-334,共10页Drugs & Clinic

基　　金：南京中医药大学自然科学基金项目(XZR2021029)。

摘　　要：目的利用网络药理学和分子对接的方法研究西黄丸治疗宫颈癌的分子机制。方法采用计算机检索TCMSP、BATMAN-TCM数据库,并筛选西黄丸的有效活性成分及作用靶点。检索OMIM、GeneCards数据库,获得宫颈癌的疾病靶点,合并去重后,与西黄丸获得的有效成分靶点取交集。运用String数据库构建蛋白质相互作用(PPI)网络图。利用Cytoscape3.9.1软件进行可视化,并采用DAVID数据库对交集基因进行(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析。最后运用AutoDock Vina、Pymol软件进行分子对接验证。结果筛选得到西黄丸70个主要活性成分,包括表雄酮、槲皮素、雄甾酮等。与宫颈癌相关的靶点有116个,核心靶点有肿瘤蛋白P53(TP53)、表皮生长因子受体(EGFR)、蛋白激酶B1(Akt1)、白细胞介素(IL)-6、原癌基因(MYC)、转录因子AP-1(JUN)、半胱氨酸蛋白酶3(CASP3)、IL-1B、肿瘤坏死因子(TNF)、雌激素受体1(ESR1)、B淋巴细胞2(Bcl-2)、低氧诱导因子-1A(HIF-1A)、基质金属蛋白酶9(MMP9)、V-Rel网状内皮增生病毒癌基因同源物A(RELA)等。GO和KEGG分析结果显示,西黄丸治疗宫颈癌的重要通路有IL-17、TNF、磷脂酰肌醇3-激酶(PI3K)/Akt、p53、HIF-1等信号通路。分子对接结果显示:西黄丸的主要成分与核心靶点有良好的对接效果。结论西黄丸主要通过调节IL-17、TNF、PI3K/Akt、p53,HIF-1等信号通路治疗宫颈癌。Objective To explore the mechanism of Xihuang Pills in treatment of cervical cancer through pharmacology network and molecular docking methods.Methods To search the active ingredients and targets of Xihuang Pills by TCMSP and BATMAN-TCM databases.To obtain the disease targets of cervical cancer OMIM and GeneCards databases.After the combination and deduplication,it intersected with the effective ingredient target obtained by Xihuang Pills.The protein interaction(PPI)network map was constructed using String database.Cytoscape 3.9.1 software was used for visualization,and the intersection genes were analyzed using DAVID database for functional enrichment(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment.Finally,AutoDock Vina and Pymol software were used to verify the molecular docking.Results Seventy main active components of Xihuang Pills were screened,including 3beta-hydroxy-5alpha-androstan-17-one,quercetin,androsterone,etc.There are 116 targets associated with cervical cancer,the core targets are TP53,EGFR,Akt1,IL-6,MYC,JUN,CASP3,IL-1B,TNF,ESR1,Bcl-2,HIF-1A,MMP9,RELA,etc.GO and KEGG analysis results showed that the important pathways of Xihuang Pills in treatment of cervical cancer were IL-17,TNF,PI3K/Akt,p53,HIF-1,and other signaling pathways.Conclusion Xihuang Pills mainly treats cervical cancer by regulating IL17,TNF,PI3K/Akt,p53,HIF-1 signaling pathways.

关 键 词：西黄丸 宫颈癌 网络药理学 分子对接 表雄酮 槲皮素 雄甾酮 肿瘤蛋白P53 白细胞介素-17 

分 类 号：R285[医药卫生—中药学]