Mechanism of "Epimedium-Cistanche deserticola" in the treatment of breast cancer with bone metastasis

Objective:"Epimedium - Cistanche deserticola" is a kind of kidney tonifying drug commonly used in the treatment of breast cancer bone metastasis, which has good clinical effect, but the pharmacological mechanism has not been fully clarified. Methods: In this study, the network pharmacology and bioinformatics technology were used to explore the mechanism of "Epimedium - Cistanche deserticola" in the treatment of breast cancer bone metastasis. TCMSP, TCM database@Taiwan and TCMID databases were used to screen the main effective components of the drug. Swiss Target Prediction and STITCH databases were used to search the potential target of action of Epimedium and Cistanche deserticola. Genecards, OMIN and Drugbank databases were used to search the cause of bone metastasis of breast cancer. The target of action of the drug and the disease gene were mapped for GO and KEGG signal pathway analysis, A visualized network of "drug - component - target - signaling pathway" was constructed by using the software of Cytoscape 3.6.0, and the core genes were screened out. Results: The study found that there are 30 main effective components of Epimedium and Cistanche deserticola, and 544 genes are involved in the potential therapeutic targets, among which 101 genes are potential targets of Epimedium and Cistanche deserticola in the treatment of breast cancer bone metastasis. Through the analysis of GO and KEGG pathways, we found that the mechanisms involved in antitumor, osteoblast differentiation, osteoclast apoptosis and regulation of bone microenvironment, such as apoptosis, osteoclast differentiation, PI3K-Akt, HIF-1 signaling pathway, T cell receptor signaling pathway, etc. TP53, VEGFA, AKT1, EGFR, SRC, CCND1, MAPK3, ESR1 may be the key genes in the treatment of breast cancer bone metastasis. Conclusion: In this study, the network of "drug - component - target- signaling pathway" was constructed through network pharmacology, and it was found that the mechanism of "Epimedium - Cistanche deserticola" in the treatment of breast cancer bone metastasis involves multiple targets and pathways, which is conducive to guiding clinical medication.

“淫羊藿-肉苁蓉”治疗乳腺癌骨转移的作用机制探讨

目的:"淫羊藿-肉苁蓉"药对是治疗乳腺癌骨转移常用补肾类药物,具有良好的临床疗效,但药理学机制尚未完全阐明,本研究应用网络药理学和生物信息学技术探讨"淫羊藿-肉苁蓉"药对治疗乳腺癌骨转移的作用机制。方法:利用TCMSP、TCM Database@Taiwan和TCMID等数据库筛选药物主要有效成分,利用Swiss Target Prediction和STITCH数据库检索淫羊藿和肉苁蓉潜在作用靶点,通过Genecards、OMIN和Drugbank数据库检索乳腺癌骨转移疾病基因,并将药物作用靶点和疾病基因进行映射,进行GO和KEGG信号通路分析,采用Cytoscape3.6.0软件构建"药物-成分-靶点-信号通路"的可视化网络,筛选出核心基因。结果:研究发现淫羊藿和肉苁蓉的主要有效成分有30种,潜在治疗靶点涉及544个基因,其中101个基因是淫羊藿和肉苁蓉治疗乳腺癌骨转移的潜在靶点;通过GO和KEGG通路分析发现作用机制涉及抗肿瘤、促进成骨细胞分化、诱导破骨细胞凋亡和调节骨微环境,如细胞凋亡、破骨细胞分化、PI3K-AKT、HIF-1信号通路、T细胞受体信号通路等。在蛋白互作网络分析中发现TP53、VEGFA、AKT1、EGFR、SRC、CCND1、MAPK3、ESR1可能是治疗乳腺癌骨转移的关键基因。结论:该研究通过网络药理学构建"药物-成分-靶向-信号通路"的网络,发现"淫羊藿-肉苁蓉"药对治疗乳腺癌骨转移作用机制涉及多靶点、多通路,有利于指导临床用药。