基于网络药理学探索锦灯笼诱导结肠癌发生铁死亡的分子机制

Molecular mechanism of Jindenglong inducing ferroptosis in colon cancer based on network pharmacology

目的基于网络药理学探究锦灯笼诱导结肠癌(colon cancer,CC)发生铁死亡的作用机制。方法通过中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)、本草组鉴(a high-throughput experiment-and reference-guided database of traditional Chinese medicine,HERB)以及Swiss Target Prediction等数据平台收集锦灯笼的主要活性成分和基因靶点。借助STRING和Metascape数据库构建锦灯笼活性成分靶基因的蛋白互作网络以及功能簇。利用Metascape网站对药物成分的靶点基因进行基因本体论(Gene Ontology,GO)功能注释和京都基因和基因组数据库(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路分析,并使用微生信作图网站进行可视化。通过Gene Cards数据库收集结肠癌疾病靶点,采用维恩图筛选出锦灯笼抑制结肠癌发生发展的潜在靶点,并进行GO和KEGG富集分析。通过FerrDb数据库收集铁死亡相关靶点,利用维恩图筛选锦灯笼治疗结肠癌与铁死亡的共同靶点,并绘制成分-铁死亡映射关系弦图。结果通过各种数据库分析筛选出了33个锦灯笼诱导结肠癌发生铁死亡的主要靶点。结论筛选出了锦灯笼诱导结肠癌发生铁死亡的潜在基因靶点。

Objective To investigate the molecular mechanism of Jindenglong induced ferrop⁃tosis in colon cancer(CC)based on network pharmacology.Methods The main active ingre⁃dients and gene targets of Jindenglong were collected through traditional Chinese Medicine Sys⁃tems Pharmacology Database and Analysis Platform(TCMSP),a high⁃throughput experiment⁃and reference⁃guided database of traditional Chinese medicine(HERB)and Swiss Target Pre⁃diction data platforms.STRING and Metascape databases were used to construct protein inter⁃action networks and functional clusters related to active ingredients in Jindenglong.Gene Ontol⁃ogy(GO)functional annotation and Kyoto Encyclopedia of genes and genomes(KEGG)and Genomespathway analysis of target genes of drug components were performed using the Metas⁃cape website and visualized using the Microbiology Letter Mapping website.Colon cancer dis⁃ease target genes were collected from the Gene Cards database,and potential targets for inhibi⁃tion of colon carcinogenesis and development by Jindenglongs were screened using Venn dia⁃grams and analyzed for GO and KEGG enrichment.Ferroptosis⁃related targets were collected through FerrDb database,and common targets of Jindenglong treatment for colon cancer and ferroptosis were screened using Venn diagram and chord diagram of component⁃ferroptosis map⁃ping relationship was drawn.Results Thirty⁃three major targets of Jindenglong induced ferrop⁃tosis in colon cancer were analyzed and screened out through various databases.Conclusion The potential gene targets of ferroptosis induced by Jindenglong in colon cancer is screened out.