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目的：基于网络药理学探讨四物汤治疗宫颈癌的作用机制。方法：通过中药系统药理学数据库与分析平台知识库收集中药活性成分，利用治疗靶点数据库、GeneCards数据库收集疾病靶点，绘制韦恩图，利用Cytoscape3.10.1构建“药物-活性成分-疾病靶点”关系网络图以及绘制蛋白质互相关系网，将交集靶点基因进行基因本体(GO)富集分析及京都基因和基因组百科全书(KEGG)通路富集分析，并应用分子对接验证药物成分与靶点之间的作用。结果：四物汤治疗宫颈癌的有效成分有106个，关键靶标51个，关键靶点包括核受体共激活因子2(PNRC2)、前列腺素内过氧化物合酶2(PTGS2)等。通过蛋白质-蛋白质相互作用(PPI)分析得到四物汤治疗宫颈癌的核心靶点，包括苏氨酸激酶1(AKT1)、肿瘤坏死因子(TNF)、PTGS2、原癌基因转录因子(JUN)及胱天蛋白酶3(CASP3)等。分子对接分析证明豆甾醇与TNF、AKT1靶点具有良好的结合活性。结论：四物汤可通过调节TNF、AKT1关键靶点发挥治疗宫颈癌的作用，为临床应用提供了一定依据。
Abstract：Objective: To study the mechanism of action of Siwu decoction in the treatment of cervical cancer based on network pharmacology. Methods: The active ingredients were collected through the traditional Chinese medicine systems pharmacology knowledge base, and the disease targets were collected by therapeutic target database and GeneCards databases. Then the Venn diagram was drawn. The "drug-active ingredient-disease target" relationship network diagram was constructed by Cytoscape 3.10.1 and the protein interrelationship network was drawn. The intersection target genes were analyzed by gene ontology(GO) and kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis. The molecular docking was used for verification. Results: There were 106 active ingredients and 51 key targets in the treatment of cervical cancer, including nuclear receptor coactivator 2(PNRC2) and prostaglandin peroxide synthase 2(PTGS2). The core targets of Siwu decoction in the treatment of cervical cancer were obtained by protein-protein interaction(PPI) analysis, including threonine kinase 1(AKT1), tumor necrosis factor(TNF), PTGS2, proto-oncogene proteins c-jun(JUN), caspase-3(CASP3), etc. Molecular docking analysis showed that stigmasterol had good binding activity with TNF and AKT1 targets. Conclusion: Siwu decoction can play a role in the treatment of cervical cancer by regulating key targets TNF and AKT1, which provides a certain basis for clinical application.
[1] Yuan Y,Cai X S,Shen F R,et al.HPV post-infection microenvironment and cervical cancer[J].Cancer Lett,2021,497:243-254.
[2] Voelker R A.Cervical cancer screening[J].JAMA,2023,330(20):2030.
[3] Perkins R B,Wentzensen N,Guido R S,et al.Cervical cancer screening:a review[J].JAMA,2023,330(6):547-558.
[4] 周燕芳，王桧，宋艳丽，等.基于“伏邪阻络，络息成积”探析子宫肌瘤的中医病机[J].环球中医药，2023,16(12):2508-2511.
[5] Chargari C,Peignaux K,Escande A,et al.Radiotherapy of cervical cancer[J].Cancer/Radiothérapie,2022,26(1/2):298-308.
[6] Mauricio D,Zeybek B,Tymon-Rosario J,et al.Immunotherapy in cervical cancer[J].Curr Oncol Rep,2021,23(6):1-12.
[7] 于俊，张立德，王建波，等.中医防治宫颈癌术后和(或)放疗后下肢淋巴水肿研究进展[J].实用中医内科杂志，2023:6.
[8] 张冠红，高丽萍，黄健妹.宫颈上皮内瘤变的研究概况及中西医结合治疗探讨[J].中国医药导刊，2021,23(12):902-906.
[9] 杨蒙婷，洪旖旎，袁媛，等.宫颈癌继发性功能障碍的危险因素分析[J].中国妇幼保健，2023,38(24):4897-4901.
[10] 王楚伊赢，陈璐，曹莹，等.宫颈癌肿瘤微环境与湿热证的相关性研究[J].中国性科学，2022,31(11):115-118.
[11] 吴诗玮，付金荣.付金荣治疗宫颈高危型人乳头瘤病毒感染经验[J].吉林中医药，2019,39(12):1566-1568.
[12] 黄昱雯，佘嫦，秦文敏.《女科指要·种子门》用药规律及诊疗思路探讨[J].基层中医药，2023,2(8):122-127.
[13] Ru J L,Li P,Wang J N,et al.TCMSP:a database of systems pharmacology for drug discovery from herbal medicines[J].J Cheminform,2014,6:13.
[14] UniProt Consortium.UniProt:a hub for protein information[J].Nucleic Acids Res,2015,43(Database issue):D204-D212.
[15] Zhou Y,Zhang Y,Zhao D,et al.TTD:therapeutic Target Database describing target druggability information[J].Nucleic Acids Res,2023:gkad751.
[16] Stelzer G,Rosen N,Plaschkes I,et al.The GeneCards suite:from gene data mining to disease genome sequence analyses[J].Curr Protoc Bioinformatics,2016,54:1.30.1-1.30.33.
[17] Bardou P,Mariette J,Escudié F,et al.Jvenn:an interactive Venn diagram viewer[J].BMC Bioinformatics,2014,15:293.
[18] Shannon P,Markiel A,Ozier O,et al.Cytoscape:a software environment for integrated models of biomolecular interaction networks[J].Genome Res,2003,13(11):2498-2504.
[19] Szklarczyk D,Gable A L,Nastou K C,et al.The STRING database in 2021:customizable protein-protein networks,and functional characterization of user-uploaded gene/measurement sets[J].Nucleic Acids Res,2021,49(D1):D605-D612.
[20] Dennis G Jr,Sherman B T,Hosack D A,et al.DAVID:database for annotation,visualization,and integrated discovery[J].Genome Biol,2003,4(9):1-11.
[21] Morris G M,Huey R,Olson A J.Using AutoDock for ligand-receptor docking[J].Curr Protoc Bioinformatics,2008,Chapter 8:Unit8.14.
[22] Wang Y L,Bryant S H,Cheng T J,et al.PubChem BioAssay:2017 update[J].Nucleic Acids Res,2017,45(D1):D955-D963.
[23] 李庆勇，姜春菲，张黎，等.β-谷甾醇、豆甾醇诱导人肝癌细胞SMMC-7721凋亡[J].时珍国医国药，2012,23(5):1173-1175.
[24] 吴力超，李俊峰，张婷婷，等.基于网络药理学和细胞实验探讨豆甾醇抗炎作用[J].中成药，2022,44(2):609-615.
[25] 辛妍，林晓转，朱璇，等.豆甾醇通过上调胆汁酸替代合成途径缓解高脂高胆固醇饮食喂养小鼠的非酒精性脂肪性肝炎[C]//第七届海峡两岸暨港澳营养科学大会摘要集，2022:39-40.
[26] 孙佳良，王佳，薛新文，等.山奈酚阻滞JAK2/STAT3通路抑制宫颈癌细胞的增殖及糖酵解的作用研究[J].药物生物技术，2023,30(4):368-373.
[27] Gao S P,Kiliti A J,Zhang K,et al.AKT1 E17K inhibits cancer cell migration by abrogating β-catenin signaling[J].Mol Cancer Res,2021,19(4):573-584.
[28] Diaz Arguello O A,Haisma H J.Apoptosis-inducing TNF superfamily ligands for cancer therapy[J].Cancers,2021,13(7):1543.
[29] Kunzmann A T,Murray L J,Cardwell C R,et al.PTGS2 (Cyclooxygenase-2) expression and survival among colorectal cancer patients:a systematic review[J].Cancer Epidemiol Biomarkers Prev,2013,22(9):1490-1497.
[30] Rahmsdorf H J.Jun:transcription factor and oncoprotein[J].J Mol Med,1996,74(12):725-747.
[31] 杨燕丽，李富娟，郭小英.翡翠贻贝多糖对宫颈癌荷瘤裸鼠免疫及抗氧化能力和p53 mRNA表达的影响[J].临床和实验医学杂志，2021,20(23):2484-2488.
[32] Sun L,Wang L F,Moore B B,et al.IL-17:balancing protective immunity and pathogenesis[J].J Immunol Res,2023,2023:1-9.
[33] Pir? B,?kof E,Smrkolj V,et al.Overview of immune checkpoint inhibitors in gynecological cancer treatment[J].Cancers,2022,14(3):631.
[34] 夏玲芳，朱俊，吴小华.2023年ESMO妇科肿瘤治疗最新进展及展望[J].中国癌症杂志，2023,33(11):969-980.
基本信息:
中图分类号:R285
引用信息:
[1]李锦湘,余田甜,李伟,等.基于网络药理学探讨四物汤治疗宫颈癌的作用机制[J].巴楚医学,2024,7(01):55-61.
基金信息:
湖北省中医药管理局2023—2024年度中医药青年人才项目(No:ZY2023Q004)
2023-12-14
2023
2024-02-05
2024
2023-12-24
1
2024-03-27
2024-03-27