基于网络药理学探讨雷公藤治疗胰腺癌的作用机制  

Mechanism of Tripterygium wilfordii in treatment of pancreatic cancer based on network pharmacology

作　　者：刘红燕 温居一[1,2] 魏晓玉 徐强 袁薪惠[4] 王保和 LIU Hong-yan;WEN Ju-yi;WEI Xiao-yu;XU Qiang;YUAN Xin-hui;WANG Bao-he(Affiliated Naval Clinical College of Anhui Medical University,Hefei ANHUI 230032,China;The Sixth Medical Center of General Hospital of the People's Liberation Army,BEIJING 100048,China;Binhai New Area Hospital of Traditional Chinese Medicine,TIANJIN 300451,China;Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine,TIANJIN 300250,China)

机构地区：[1]安徽医科大学海军临床学院,安徽合肥230032 [2]中国人民解放军总医院第六医学中心,北京100048 [3]天津市滨海新区中医医院,天津300451 [4]天津中医药大学第二附属医院,天津3300250

出　　处：《中国新药与临床杂志》2022年第10期622-628,共7页Chinese Journal of New Drugs and Clinical Remedies

基　　金：国家重点研发计划(2018YFC1707404);军队后勤科研计划重点项目(BHJ14C008)。

摘　　要：目的 通过网络药理学方法探讨雷公藤治疗胰腺癌的作用机制。方法 通过中药系统药理学分析平台(TCMSP)数据库获取雷公藤的活性成分及对应靶点,通过GeneCards、TTD数据库获取胰腺癌的靶点基因,对两者取交集获取胰腺癌相关的雷公藤活性成分作用靶点。应用ClusterProfiler进行基因本体(GO)富集,通过Cytoscape 3.8软件进行京都基因与基因组百科全书(KEGG)通路富集并筛选活性成分-靶点核心网络,使用Autodock Vina和Discovery studio软件进行分子对接和可视化。结果 雷公藤活性成分与疾病的交集靶点114个。GO富集和KEGG通路富集分析表明雷公藤治疗胰腺癌的作用机制可能与凋亡、核因子(NF)-κB、缺氧诱导因子(HIF)-1、血管内皮生长因子(VEGF)、白细胞介素(IL)-17等有关。5个药物活性成分(雷酚新内酯、雷公藤宁B、雷酚内酯、雷酚萜醇、雷酚萜)和7个核心靶点(TOP2A、ADRB2、KCNH2、PGR、HSP90AA1、AKT1、TNF)构成核心网络,生存分析显示TOP2A、KCNH2、PGR、HSP90AA1、AKT1、TNF高表达的患者预后较差(P <0.05)。分子对接结果显示关键活性成分与核心靶点结合性较好。结论 雷公藤可通过雷酚新内酯、雷公藤宁B等活性成分作用于TOP2A、ADRB2、KCNH2等靶点治疗胰腺癌,其机制可能与凋亡、NF-κB、HIF-1、VEGF、IL-17等相关通路有关。AIM To explore the mechanism of Tripterygium wilfordii in the treatment of pancreatic cancer by network pharmacology. METHODS The active components and corresponding targets of Tripterygum wilfordii were obtained through Traditional Chinese Medicine Systems Pharmacology Database( TCMSP), and related targets of pancreatic cancer were obtained through Genecards and TTD database. Then the intersection targets were obtained by integrating the drug targets and disease targets. Gene Ontology( GO) enrichment analysis was carried out using ClusterProfiler. Kyoto Encyclopedia of Genes and Genomes( KEGG) pathway enrichment analysis and screening of active ingredient-target core networks were carried out using Cytoscape 3.8 software. Molecular docking was carried out using Autodock Vina and Discovery studio software. RESULTS One hundred and fourteen drug and disease intersection targets were obtained. GO enrichment analysis and KEGG pathway enrichment analysis indicated that the mechanism of Tripterygium wilfordii in the treatment of pancreatic cancer may be related to apoptosis, nuclear factor( NF)-κB, hypoxia-inducing factors( HIF)-1, vascular endothelial growth factor( VEGF), interleukin( IL)-17 and so on. The core network was composed of 5 main components( neotriptophenolide, triptinin B, tryptophenolide, triptonoterpenol, triptonoterpene) and 7 core targets( TOP2A, ADRB2, KCNH2, PGR, HSP90AA1, AKT1, TNF), which were all highly expressed in pancreatic cancer tissues. The survival analysis showed that the patients with high expression of TOP2A, KCNH2, PGR, HSP90AA1, AKT1 and TNF had poor prognosis( P < 0.05). Molecular docking showed that the main components had good binding properties with the core protains. CONCLUSION Tripterygium wilfordii can act on TOP2A, ADRB2, KCNH2 and other targets through the active components such as neotriptophenolide and triptinin B in the treatment of pancreatic cancer, and its mechanism related to regulating apoptosis, NF-κB, HIF-1, VEGF, IL-17 and other signaling pathways.

关 键 词：雷公藤 胰腺肿瘤 网络药理学 分子对接模拟 

分 类 号：R736.7[医药卫生—肿瘤] R979.1[医药卫生—临床医学]