基于网络药理学和分子对接的石菖蒲苷在子宫内膜癌治疗中的机制研究
Mechanism of salidroside in the treatment of endometrial cancer based on network pharmacology and molecular docking.
发表日期:2023 Aug 29
作者:
Panpan Yang, Yihong Chai, Min Wei, Yan Ge, Feixue Xu
来源:
CLINICAL PHARMACOLOGY & THERAPEUTICS
摘要:
盐酸酰胺是酚类的一种天然产物,具有广泛的药理作用,但其对子宫内膜癌的药理作用和分子机制尚不清楚。通过网络药理学的方法,系统探索盐酸酰胺在子宫内膜癌上的药理作用和分子机制。通过不同的药理学数据库和分析平台得到盐酸酰胺的可能靶基因,然后通过GeneCards网站获得子宫内膜癌的相关靶基因,并统一将靶基因转化为标准化基因名。然后对收集到的数据进行处理,得到共同的靶基因,并通过String网站进一步分析得到蛋白质相互作用网络(PPI),随后进行基因本体论(GO)功能注释和Kyoto基因和基因组百科全书(KEGG)途径分析。通过构建“药物成分-靶基因-疾病”网络进一步解释了盐酸酰胺治疗子宫内膜癌的分子机制。最后进行了分子对接实验证明盐酸酰胺与候选靶基因具有高亲和力。经过归一化处理后,盐酸酰胺有175个靶基因,其中113个与子宫内膜癌有相互作用。GO分析表明盐酸酰胺的抗子宫内膜癌作用可能与凋亡和对药物的反应等生物过程密切相关。KEGG分析表明其机制可能与癌症通路和PI3K-AKT信号通路有关。分子对接结果显示盐酸酰胺与五个关键基因具有高亲和力。基于创新的网络药理学和分子对接验证研究方法,我们首次揭示了盐酸酰胺在治疗子宫内膜癌中的潜在机制。© 2023. Springer Nature Limited.
Salidroside is a natural product of phenols, which has a wide scape of pharmacological effects, but its pharmacological effects and molecular mechanism on endometrial cancer are not clear. To systematically explore the pharmacological effects and molecular mechanisms of salidroside on endometrial cancer through the method of network pharmacology. The possible target genes of salidroside were obtained through different pharmacological databases and analysis platforms, and then the relevant target genes of endometrial cancer were obtained through the GeneCards website, and the target genes were uniformly converted into standardized gene names with Uniprot. The collected data were then processed to obtain common target genes and further analyzed through the String website to construct a protein-protein interaction (PPI) network, followed by gene ontology (GO) functional annotation and Kyoto Gene and Genome Encyclopedia (KEGG) pathway analysis. We further interpreted the molecular mechanism of salidroside for the treatment of endometrial cancer by constructing a "drug component-target gene-disease" network. Finally, we performed molecular docking to validate the binding conformation between salidroside and the candidate target genes. There were 175 target genes of salidroside after normalization, among which 113 target genes interacted with endometrial cancer. GO analysis indicated that the anti-endometrial cancer effect of salidroside may be strongly related to biological processes such as apoptosis and response to drug. KEGG analysis indicated that its mechanism may be related to pathway in cancer and PI3K-AKT signaling pathway. Molecular docking showed that salidroside had high affinity with five key genes. Based on the novel network pharmacology and molecular docking validation research methods, we have revealed for the first time the potential mechanism of salidroside in the therapy of endometrial cancer.© 2023. Springer Nature Limited.