基于网络药理学、分子对接和双样本孟德尔随机化分析探讨槐耳抗胰腺癌的作用机制

doi:10.16139/j.1007-9610.2025.03.11

摘要/Abstract

摘要：

目的：探索槐耳抗胰腺癌的作用机制。方法：通过Herb数据库检索槐耳的化合物成分和靶点，通过GeneCards、NCBI、DisGeNET等在线数据库筛选胰腺癌相关靶点，绘制韦恩图获取药物与疾病交集靶点。采用String平台构建蛋白质-蛋白质相互作用（PPI）网络，利用Cytoscape3.8.0软件构建一系列网络图来筛选核心靶点并对靶基因进行GO分析和KEGG通路富集分析，最后通过AutoDock软件对关键活性成分与潜在作用靶点进行分子对接验证。使用Open GWAS数据库中的KEGG富集top20通路的基因和胰腺癌的全基因组关联分析数据进行孟德尔随机化分析进一步验证。结果：共筛选出4个槐耳有效成分，药物与疾病交集靶点112个。主要活性成分为山奈酚、芦丁、染料木素、葡萄糖醛酸，核心靶点为促分裂原活化蛋白激酶8（MAPK8）、尿苷二磷酸（UDP）-葡萄糖醛酸转移酶1家族多肽A1（UGT1A1）、超氧化物歧化酶2（SOD2）。作用机制可能与胰腺癌、肿瘤坏死因子（TNF）信号通路、白细胞介素（IL）-17信号通路等有关。分子对接显示主要活性成分与关键靶点具有很好的对接活性。经筛选保留了73个基因，24 195 229个单核苷酸多态性（SNP）用于双样本孟德尔随机化分析，分析结果表明，MAPK8可能是胰腺癌的重要治疗靶点。结论：槐耳可能通过作用于MAPK8产生抗胰腺癌的作用，为进一步验证槐耳治疗胰腺癌的作用机制提供了初步的理论依据。

关键词: 槐耳, 胰腺癌, 网络药理学, 分子对接, 孟德尔随机化分析

Abstract:

Objective To explore the mechanism of action of Huaier (Vanderbylia robiniophila) against pancreatic cancer. Methods The chemical components and targets of Huaier (Vanderbylia robiniophila) were searched through the Herb database. Pancreatic cancer-related targets were screened from GeneCards, NCBI, and DisGeNET online databases, and a Venn diagram was drawn to obtain the intersection targets of drugs and diseases. The protein-protein interaction (PPI) network was constructed using the String platform, and a series of network diagrams were drawn using Cytoscape 3.8.0 software to screen core targets and perform GO analysis and KEGG pathway enrichment analysis on the target genes. Finally, the key active components were molecularly docked with potential target genes using AutoDock software. The KEGG enrichment top 20 pathways and the whole-genome association analysis data of pancreatic cancer were used to further validate the results using the Open GWAS database through Mendelian randomization analysis. Results A total of 4 effective components of Huaier (Vanderbylia robiniophila) were identified, 112 drug-disease intersection targets, the main active components were kaempferol, rutin, genistein, and glucuronic acid, and the core targets were mitogen-activated protein kinase 8 (MAPK8), uridine diphosphate(UDP)-glucuronic acid transferase 1 family peptide A1 (UGT1A1), and superoxide dismutase 2 (SOD2). The mechanism of action may be related to pancreatic cancer, tumor necrosis factor(TNF) signaling pathway, and interleukin(IL)-17 signaling pathway. The molecular docking showed that the main active components had good docking activity with the key targets. After screening, 73 genes were retained, and 24,195,229 single nucleotide polymorphism(SNP) were used for two-sample Mendelian randomization analysis. The analysis results showed that MAPK8 may be an important therapeutic target for pancreatic cancer. Conclusions Huaier (Vanderbylia robiniophila) may exert an anti-pancreatic cancer effect by acting on MAPK8, providing initial theoretical evidence for further verifying the mechanism of action of Huaier in treating pancreatic cancer.

Key words: Huaier (Vanderbylia robiniophila), Pancreatic cancer, Network pharmacology, Molecular docking, Mendelian randomization analysis

中图分类号:

R735.9

金佳斌, 马君俊, 叶枫, 马诗瑜, 陈敬贤. 基于网络药理学、分子对接和双样本孟德尔随机化分析探讨槐耳抗胰腺癌的作用机制[J]. 外科理论与实践, 2025, 30(03): 247-255.

JIN Jiabin, MA Junjun, YE Feng, MA Shiyu, CHEN Jingxian. Investigation of the mechanism of Huaier (Vanderbylia robiniophila) anti-pancreatic cancer based on network pharmacology, molecular docking, and two-sample Mendelian randomization analysis[J]. Journal of Surgery Concepts & Practice, 2025, 30(03): 247-255.

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Name	Average shortest path length	Betweenness centrality	Closeness centrality	Degree
Genistein	1.547 008 55	0.255 887	0.646 409	83
Kaempferol	2.111 111 11	0.087 602	0.473 684	50
Rutin	2.794 871 79	0.004 041	0.357 798	10
Glucuronic acid	2.846 153 85	0.001 373	0.351 351	7

Cluster	Nodes	Edges	Node IDs
1	53	1 137	SIRT1, INS, CDKN1A, PPARG, BCL2, PTGS2, CXCL1,MAPK8, CDK1, PPARA, TNF, GSK3B,STAT3, MMP9, PTEN, JUN, AKT1, ESR1, STAT1, RELA, FN1, CASP9, NOS2, AR, PGR, MMP1, CASP3, CXCL8, FOS, VCAM1, ATM, EGFR, ERBB2, TP53, CDK2, ICAM1, IL1B, MAPK3, MDM2, CCNB1, CCNA2, MAPK14, IGF1R, IFNG, CCL2, MPO, HIF1A, IKBKB, TGFB1, TIMP1, CDKN2A, HMOX1, MAPK1
2	5	9	NR1I2, GSTM1, UGT1A1, CYP1A2, CYP1B1
3	5	6	SOD1, SLC2A4, PPARGC1A, HMGCR, SOD2

Protein and PDB ID	Genistein	Glucuronic acid	Kaempferol	Rutin
MAPK8（3ELJ）	-8.5	-5.3	-8.2	-7.9
UTG1A1（AF-P22309-F1）	-8.2	-5.6	-8.3	-9.8
SOD2（1PL4）	-7.5	-5.1	-7.9	-8.2