Heilongjiang University of Chinese Medicine, Harbin, 150000, China.
The First Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin, 150000, China.
Comb Chem High Throughput Screen. 2024;27(17):2583-2597. doi: 10.2174/0113862073266004231105164321.
Yishan formula (YSF) has a significant effect on the treatment of breast cancer, which can improve the quality of life and prolong the survival of patients with breast cancer; however, its mechanism of action is unknown.
In this study, network pharmacology and molecular docking methods have been used to explore the potential pharmacological effects of the YSF, and the predicted targets have been validated by in vitro experiments.
Active components and targets of the YSF were obtained from the TCMSP and Swiss target prediction website. Four databases, namely GeneCards, OMIM, TTD, and DisGeNET, were used to search for disease targets. The Cytoscape v3.9.0 software was utilized to draw the network of drug-component-target and selected core targets. DAVID database was used to analyze the biological functions and pathways of key targets. Finally, molecular docking and in vitro experiments have been used to verify the hub genes.
Through data collection from the database, 157 active components and 618 genes implicated in breast cancer were obtained and treated using the YSF. After screening, the main active components (kaempferol, quercetin, isorhamnetin, dinatin, luteolin, and tamarixetin) and key genes (, and ) were obtained. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that the YSF could affect the progression of breast cancer by regulating biological processes, such as signal transduction, cell proliferation and apoptosis, protein phosphorylation, as well as PI3K-Akt, Rap1, MAPK, FOXO, HIF-1, and other related signaling pathways. Molecular docking suggested that IL6 with isorhamnetin, MAPK3 with kaempferol, and EGFR with luteolin have strong binding energy. The experiment further verified that YSF can control the development of breast cancer by inhibiting the expression of the hub genes.
This study showed that resistance to breast cancer may be achieved by the synergy of multiple active components, target genes, and signal pathways, which can provide new avenues for breast cancer-targeted therapy.
抑癌方（YSF）对乳腺癌的治疗有显著疗效，能提高乳腺癌患者的生活质量并延长其生存时间，但作用机制尚不明确。
采用网络药理学和分子对接的方法，探讨 YSF 的潜在作用机制，并通过体外实验对预测靶点进行验证。
从 TCMSP 数据库和瑞士药物靶点预测网站获取 YSF 的活性成分和作用靶点，借助 GeneCards、OMIM、TTD 和 DisGeNET 数据库，搜索疾病靶点，运用 Cytoscape v3.9.0 软件绘制药物-成分-靶点网络图，筛选出核心靶点，运用 DAVID 数据库对关键靶点进行生物功能和通路分析，最后采用分子对接和体外实验对核心基因进行验证。
通过数据库收集，得到 YSF 治疗乳腺癌的 157 个活性成分和 618 个作用靶点，经筛选后获得主要活性成分（山奈酚、槲皮素、异鼠李素、地奥司明、木樨草素、杨梅素）和关键基因（AKT1、IL6、MAPK3），GO 功能和 KEGG 通路富集分析结果表明，YSF 可能通过调控信号转导、细胞增殖和凋亡、蛋白磷酸化及 PI3K-Akt、Rap1、MAPK、FOXO、HIF-1 等相关信号通路影响乳腺癌的发生发展，分子对接提示异鼠李素与 IL6、山奈酚与 MAPK3、木樨草素与 EGFR 具有较强的结合能，实验进一步验证了 YSF 通过抑制核心基因的表达调控乳腺癌的发生发展。
本研究表明 YSF 可能通过多成分、多靶基因、多信号通路协同作用来抑制乳腺癌的发生发展，为乳腺癌的靶向治疗提供新的思路。
