基于网络药理学和分子对接技术探讨郁金治疗乳腺癌的作用机制

Exploring the mechanism of Yujin in the treatment of breast 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讨郁金治疗乳腺癌的分子机制。方法利用中药系统药理学分析平台(TCMSP)检索筛选郁金的有效成分,查询有效成分作用的靶点,利用UniversalProtein数据库(Uniprot)进行靶点注释;在Genecards和人类孟德尔遗传综合数据库(OMIM)检索乳腺癌相关基因;绘制有效成分作用靶点和乳腺癌相关基因的维恩图;使用Cytoscape3.7.2软件构建郁金-有效成分-靶点-乳腺癌网络;使用STRING平台构建蛋白互助网络(PPI network),并获取核心基因;运用Bioconductor进行GO生物过程富集及KEGG信号通路预测;运用Autodock vina软件对有效成分和靶点进行分子对接。结果郁金筛选出有效成分15种,有效成分对应作用靶点78个,与乳腺癌交集靶点49个,预测郁金作用于乳腺癌主要成分为柚皮素(naringenin)、β-谷甾醇(beta-sitosterol)、谷甾醇(sitosterol),核心基因为AKT1、MAPK3等,GO功能主要涉及磷酸酶结合、G蛋白偶联胺受体活性、抗氧化活性等过程,KEGG信号通路4条,柚皮素、β-谷甾醇与蛋白靶点对接示具有较强结合能力。结论郁金对乳腺癌具有一定的治疗作用,其有效成分柚皮素、β-谷甾醇与AKT1等多靶点结合抗乳腺癌的机制,可以为后续实验研究提供理论依据。

Objective To explore the molecular mechanism of Yujin in the treatment of breast cancer based on network pharmacology and molecular docking technology.Methods The active ingredients and the targets of Yujin were collected by the TCM System Pharmacology Analysis Platform(TCMSP).Annotated the targets by using the Universal Protein database(Uniprot).Found the breast cancer related genes from the Genecards and the Human Mendelian Genetic Database(OMIM).Identified the target of all potential active ingredients and built the“active ingredient target”networ by using the software of Cytoscape 3.7.2.Obtained core genes and built the protein mutual aid network(PPI network)by the STRING platform.Used Bioconductor for GO biological process enrichment and KEGG signal pathway prediction.Finally used Autodock vina software to do molecular docking of active ingredients and targets.Results 15 kinds of active ingredients were screened out for turmeric,which corresponded to 78 target points and 49 targets that intersect breast cancer.It is predicted that the main components of Yujin on breast cancer including naringenin、β-sitosterol(beta-sitosterol)and sitosterol.The core genes are AKT1,MAPK3,etc.The function of GO mainly involves processes such as phosphatase binding,G protein-coupled amine receptor activity,and antioxidant activity.There are 4 KEGG signal pathways.The docking of naringenin and β-sitosterol with protein targets showed that they have strong binding ability.Conclusion Yujin has a certain therapeutic effect on breast cancer.Its effective ingredients such as naringenin,β-sitosterol can combine with multiple targets to resist breast cancer,which can provide a theoretical basis for subsequent experimental studies.