摘要
目的:应用GEO数据库、TCMSP中药数据库和分析平台、TCGA临床数据库,采用分子对接技术研究藏药八味沉香散抗乳腺癌的有效成分和分子机制。方法:采用TCMSP中药数据库和分析平台检索藏药八味沉香散的有效成分和作用靶点;从GEO数据库下载乳腺癌芯片数据,通过R软件中的limma程序包筛选差异基因,利用Jvenn和Cytoscape 3.7.2软件筛选藏药八味沉香散与乳腺癌的交集靶点,构建蛋白互作网络,并对核心靶点进行GO功能、KEGG通路富集、关键基因的表达量及预后关联性分析。进一步采用AutoDockTools 1.5.6及AutoDock Vina软件进行分子对接,验证活性成分与核心靶点的结合能力。结果:检索得到藏药八味沉香散抗乳腺癌有效成分59个,核心靶点5个。GO功能主要富集到镉离子反应、金属离子反应、细胞周期蛋白依赖性蛋白激酶全酶复合物、RNA聚合酶Ⅱ转录因子复合物、氧化还原酶活性、蛋白磷酸酶结合等。KEGG通路富集主要集中在分泌抵抗、Toll样受体信号通路、乳腺癌、类风湿性关节炎、IL-17信号通路等。分子对接结果显示AKT1蛋白与活性成分lappadilactone之间形成了氢键,且对接分值最低,结合较稳定。结论:藏药八味沉香散中的有效成分槲皮素、木犀草素、山柰酚等作用于核心靶点HSPA5、AKT1、PCNA、CDK1、JUN,通过调控乳腺癌细胞凋亡、增殖、迁移、侵袭的信号通路进而发挥抗乳腺癌的作用。
Objective To study the active ingredients and molecular mechanism of Tibetan medicine A′kar Gyad⁃pa against breast cancer by applying GEO database,TCMSP Chinese medicine database and analysis platform,TCGA clinical database and molecular docking technology.Methods The active ingredients and action targets of Tibetan medicine A′kar Gyadpa were retrieved by using TCMSP Chinese medicine database and analysis plat⁃form;the breast cancer microarray data were downloaded from GEO database,the differential genes were screened by limma package in R software,the intersection targets of Tibetan medicine A′kar Gyadpa and breast cancer and the protein interaction network were constructed by using Jvenn and Cytoscape 3.7.2 software.The core targets were analyzed by GO function,KEGG pathway enrichment,expression of key genes and prognostic relevance.Further,molecular docking was performed using AutoDockTools 1.5.6 and AutoDock Vina software to verify the binding ability of the active ingredients to the core targets.Results The search found 59 active ingredi⁃ents and 5 core targets of Tibetan medicine A′kar Gyadpa against breast cancer.GO functions were mainly en⁃riched to cadmium ion response,metal ion response,cell cycle protein-dependent protein kinase holoenzyme complex,RNA polymerase II transcription factor complex,oxidoreductase activity,and protein phosphatase bind⁃ing.KEGG pathway enrichment was mainly focused on secretion resistance,Toll-like receptor signaling path⁃way,breast cancer,rheumatoid arthritis,IL-17 signaling pathway,etc.The molecular docking results showed that the AKT1 protein formed hydrogen bonds with the active ingredient lappadilactone,and the docking fraction was the lowest,and the binding was more stable.Conclusions The active ingredients quercetin,lignan and kaempferol in Tibetan medicine A′kar Gyadpa act on the core targets HSPA5,AKT1,PCNA,CDK1 and JUN,and then exert anti-breast cancer effects by regulating the signaling pathways of apoptosis,proliferation,migra⁃tion and inva
作者
万玛措
仁增加
切羊让忠
贡却坚赞
Wanma-Cuo;Renzeng-Jia;Qieyang-Rangzhong;Gongque-Jianzan(Tibetan Medical College,Qinghai University,Xining 810016,China;State Key Laboratory of Tibetan medicine research and development,Xining 810016,China)
出处
《高原科学研究》
CSCD
2021年第4期74-83,共10页
Plateau Science Research
基金
青海省科技厅项目(2020-ZJ-776)
青海大学专业核心课程项目(ZYHX-202113)。
