中医肿瘤学杂志2024，Vol.6Issue(2)：49-57,67,10.DOI:10.19811/j.cnki.ISSN2096-6628.2024.03.007
基于网络药理学、分子对接及实验验证探讨大黄素治疗乳腺癌合并高脂血症的作用机制
Mechanism of Emodin in Treating Breast Cancer Complicated with Hyperlipidemia Based on Network Pharmacology,Molecular Docking,and Experimental Verification
摘要
Abstract
Objective Based on network pharmacology,the targets and signal pathways of emodin in the treatment of breast cancer complicated with hyperlipidemia were preliminically predicted,and the possible mechanisms of emodin were investigated through molecular docking and in vitro experiment.Methods Emodin targets were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and Swiss Target Prediction database.The relevant targets of breast cancer and hyperlipidemia were obtained from GeneCards and OMIM databases,respectively.The common targets of emodin,breast cancer,and hyperlipidemia were obtained using the online software Venny software,and common targets were used to construct a protein-protein interaction(PPI)network in the STRING database.Visual analysis and core target screening were performed using Cytoscape 3.9.1 software.Gene Ontology(GO)biological process and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were conducted using the Metascape online gene function annotation analysis tool.Molecular docking validation was performed using software such as AutoDock Vina for the key targets and emodin.The role of emodin in inhibiting breast cancer development was detected in breast cancer 4T1 cells and tumor-associated macrophage(TAM).The effects of emodin on the growth of 4T1 cells were detected by CCK-8 and the optimal concentration was screened.The expression levels of matrix metalloproteinase 9(MMP9),interleukin-1beta(IL-1β),and transforming growth factor beta 1(TGF-β1)were detected by Real-time PCR and ELISA,respectively.Results A total of 43 common targets related to emodin,breast cancer,and hyperlipidemia were obtained,including core targets such as tumor protein p53(TP53),tumor necrosis factor(TNF),myelocytomatosis oncogene(MYC),epidermal growth factor receptor(EGFR),heat shock protein 90kDa alpha1(HSP90AA1),and caspase 3(CASP3).These targets involved in various pathways such as cancer pathways,chemical carcinogenesis-receptor activation,lipids and atherosclerosis,bladder cancer,colorectal cancer,proteoglycans in cancer,and the interleukin-17(IL-17)signaling pathway.Molecular docking confirmed that emodin exhibited strong binding activity with the core targets.Additionally,experimental results demonstrated that emodin significantly downregulated the expression of MMP9 and TGF-β1 in 4T1 cells.Furthermore,emodin reduced the IL-1β expression induced by co-culture of TAM and lipopolysaccharide(LPS).Conclusion The mechanism of emodin in the treatment of breast cancer complicated with hyperlipidemia may be related to the inhibition of tumor cell proliferation and metastasis,induction of tumor cell apoptosis,and regulation of the inflammatory microenvironment associated with both tumor and hyperlipidemia.关键词
大黄素/网络药理学/分子对接/乳腺癌/高脂血症Key words
emodin/network pharmacology/molecular docking/breast cancer/hyperlipidemia分类
医药卫生引用本文复制引用
张素方,李海霞,刘清清,王大伟,刘擎..基于网络药理学、分子对接及实验验证探讨大黄素治疗乳腺癌合并高脂血症的作用机制[J].中医肿瘤学杂志,2024,6(2):49-57,67,10.基金项目
广州市科技计划项目(编号:2060206). （编号:2060206）
