基于网络药理学探究桂枝茯苓丸治疗宫颈癌的作用机制

Exploring the Mechanism of Guizhi Fuling Pills in the Treatment of Cervical Cancer Based on Network Pharmacology

摘要: 目的：探究桂枝茯苓丸治疗宫颈癌的作用机制。方法：利用TCMSP数据库筛选桂枝茯苓丸中各药物的活性化合物及靶点。利用Gene Cards数据库检索宫颈癌的疾病靶点，根据药物靶点与疾病靶点构建桂枝茯苓丸活性化合物靶点与疾病靶点的Venn图、化合物–靶点相互作用网络图、PPI网络图，并进行GO功能富集分析和KEGG通路富集分析。结果：筛选出桂枝茯苓丸中共69个活性化合物，对应宫颈癌274个靶点，通过数据分析得出，桂枝茯苓丸治疗宫颈癌的核心有效活性成分有山柰酚、β-谷固醇、常春藤皂苷元、槲皮素、聚孔酸C、啤酒甾醇、氢化松苓酸、儿茶素等，其治疗宫颈癌的核心靶点有PTPN1、HMGCR、CYP19A1、NR3C1、PTGS2、PTPN2、PTGES等；通过交集靶点PPI分析得出桂枝茯苓丸治疗宫颈癌核心靶标为TP53、非受体酪氨酸激酶、丝裂原激活蛋白激酶3、连环蛋白β1、苏氨酸激酶1、表皮生长因子受体及血管内皮生长因子A等；涉及的反应有蛋白质磷酸化、细胞凋亡过程的负调控、肽基酪氨酸磷酸化及对外源刺激的反应等；细胞过程涉及的部分有细胞质、质膜、膜筏及受体复合物等；分子过程涉及到蛋白丝氨酸/苏氨酸/酪氨酸激酶活性、蛋白酪氨酸激酶活性、ATP结合及跨膜受体蛋白酪氨酸激酶活性等；涉及的关键信号通路有PI3K-Akt信号通路、蛋白多糖在癌症中的作用、脂质与动脉粥样硬化及EGFR酪氨酸激酶抑制剂耐药等。结论：桂枝茯苓丸中活性化合物可以通过关键靶点调控机体的应激反应及免疫反应达到治疗宫颈癌的效果，是多成分、多靶点、多途径相互作用的结果，为桂枝茯苓丸更好地应用于临床提供一定的理论依据。

Abstract: Objective: To explore the mechanism of Guizhi Fuling pills in treating cervical cancer. Methods: The active compounds and targets of each drug in Guizhi Fuling Pills were screened through the TCMSP database. The Gene Cards database was used to search the disease targets of cervical cancer, and the Venn diagram, the compound-target interaction network diagram, and the PPI network dia-gram of the active compound targets and disease targets of Guizhi Fuling Pills were constructed ac-cording to the drug targets and disease targets. GO functional enrichment analysis and KEGG path-way enrichment analysis were performed. Results: A total of 69 active compounds in Guizhi Fuling pills were screened out, corresponding to 274 targets of cervical cancer. Through data analysis, it was concluded that the core effective active ingredients of Guizhi Fuling pills in the treatment of cervical cancer are kaempferol and β-sitosterol, hedera saponin, quercetin, polyporic acid C, Cere-visterol, hydropine pinic acid, catechin, etc., and its core targets for the treatment of cervical cancer include PTPN1, HMGCR, CYP19A1, NR3C1, PTGS2, PTPN2, PTGES et al. Through the analysis of in-tersection target PPI, it is concluded that the core targets of Guizhi Fuling Pills in the treatment of cervical cancer are TP53, non-receptor tyrosine kinase, mitogen-activated protein kinase 3, catenin β1, threonine kinase 1, epidermis Growth factor receptors and vascular endothelial growth factor A, etc.; the reactions involved include protein phosphorylation, negative regulation of apoptosis pro-cess, peptidyl tyrosine phosphorylation and response to external stimuli, etc.; the part involved in cell processes includes cytoplasm , plasma membrane, membrane rafts and receptor complexes, etc.; molecular processes involving protein serine/threonine/tyrosine kinase activity, protein tyro-sine kinase activity, ATP binding and transmembrane receptor protein tyrosine kinase activity etc.; the key signaling pathways involved include PI3K-Akt signaling pathway, the role of proteoglycan in cancer, lipids and atherosclerosis, and EGFR tyrosine kinase inhibitor resistance, etc. Conclusion: The active compounds in Guizhi Fuling Pills can regulate the body’s immune response and stress response to treat cervical cancer through key targets. It provides a certain theoretical basis for clin-ical application.