基于网络药理学和分子对接技术探究脾积丸治疗胰腺癌的分子机制

Mechanism of Piji Pills in treatment of pancreatic cancer based on network pharmacology and molecular docking technology

目的基于网络药理学和分子对接技术探究脾积丸治疗胰腺癌的潜在通路与物质基础。方法以口服生物利用度(OB)≥30%与类药性(DL)≥0.18为筛选条件,在中药系统药理学平台(TCMSP)数据库获取脾积丸主要活性成分及关键靶点,利用GeneCards、OMIM、PharmGkb和TDD数据库获得胰腺癌主要靶点;绘制Venn图,构建主要成分–关键靶点网络图,绘制蛋白互作(PPI)网络;进行基因本体(GO)功能及京都基因与基因组百科全书(KEGG)通路富集分析,最后以分子对接来验证所得靶点。结果筛选得到32个活性成分,预测获得210个靶点,核心基因17个;脾积丸治疗胰腺癌的活性成分是槲皮素、山柰酚、柚皮素、芒柄花黄素、川陈皮素。GO功能富集分析得到生物过程(BP)2409个、细胞组成(CC)91个、分子功能(MF)14个;KEGG通路富集分析获得179条通路。核心成分与主要核心靶点有一定的结合活性,其中槲皮素与HIF1A靶点对接活性最好。结论脾积丸可通过多成分、多靶点和多通路发挥治疗胰腺癌的作用,为后续探究脾积丸治疗胰腺癌提供研究思路。

Objective To explore the potential pathway and material basis of Piji Pills in treatment of pancreatic cancer based on network pharmacology and molecular docking technology.Methods With OB≥30%and DL≥0.18 as screening conditions,the main active components and key targets of Piji Pills were obtained from TCMSP database,and the main targets of pancreatic cancer were obtained by GeneCards,OMIM,PharmGkb and TDD database.Venn diagram,key target network map and protein interaction network(PPI)were drawn.GO enrichment analysis and KEGG pathway enrichment analysis were carried out.Finally,molecular docking was used to verify the target.Results 32 Active components were screened,and 210 targets were predicted with 17 core genes.The active ingredient of Piji Pills in treatment of pancreatic cancer were quercetin,kaempferol,naringin,formononetin,anthocyanin,and tangerine.Furthermore,2409 BP terms,91 CC terms and 14 MF terms were obtained with GO function enrichment analysis.Moreover,179 relative pathways were obtained with KEGG pathway enrichment analysis.The core components had certain binding activity with the main core targets,among which quercetin had the best docking activity with HIF1A target.Conclusion Piji Pills plays a role in treatment of pancreatic cancer through multi-component,multi-target and multi-channel,which provides a research idea for follow-up study of Piji pills in treatment of pancreatic cancer.