研究动态
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基于网络药理学和分子对接研究,探究黄水仙碱在治疗胶质母细胞瘤中的分子机制。

Molecular mechanism of lycorine in the treatment of glioblastoma based on network pharmacology and molecular docking.

发表日期:2023 Sep 05
作者: Jie Su, Mengmeng Huo, Fengnan Xu, Liqiong Ding
来源: CLINICAL PHARMACOLOGY & THERAPEUTICS

摘要:

利可君(Lycorine)是一种天然活性生物碱,已被证明对多种癌症具有抑制作用。然而,利可君在治疗胶质母细胞瘤(GBM)中的潜在机制尚不清楚。本研究基于网络药理学和分子对接技术,探究了利可君在GBM治疗中的机制。利可君相关靶点与GBM相关靶点发生重叠,获得代表利可君潜在抗GBM靶点的交集。利用STRING在线数据库构建蛋白质相互作用(PPI)网络,并通过Cytoscape软件进行分析得出10个关键靶基因(AKT1、SRC、HSP90AA1、HRAS、MMP9、BCL2L1、IGF1、MAPK14、STAT1和KDR),它们在利可君对GBM的治疗效果中起重要作用。基因本体论(GO)和Kyoto基因与基因组百科全书(KEGG)富集分析表明,利可君通过多条途径作用于GBM,包括诱导凋亡和产生活性氧自由基。分子对接结果表明利可君与这10个关键基因具有强大的结合效率。此外,我们发现利可君诱导U-87 MG胶质母细胞瘤细胞凋亡。本研究详细阐明并通过实验证实了利可君对GBM的作用机制,为其临床应用提供了证据支持。© 2023. 作者在Springer-Verlag GmbH Germany(德国施普林格出版公司)的独家许可下,属于Springer Nature的一部分。
Lycorine is a naturally active alkaloid that has been shown to have inhibitory effects on a variety of cancers. However, the underlying mechanism of lycorine in the treatment of glioblastoma (GBM) is unclear. In this study, we investigated the mechanism of lycorine in the treatment of GBM based on network pharmacology and molecular docking. Lycorine-related targets overlapped with GBM-related targets to obtain intersections that represent potential anti-GBM targets for lycorine. The protein-protein interaction (PPI) network was constructed using the STRING online database and analyzed by Cytoscape software, and 10 key target genes (AKT1, SRC, HSP90AA1, HRAS, MMP9, BCL2L1, IGF1, MAPK14, STAT1, and KDR) were obtained, which played an important role in the therapeutic effect of lycorine on GBM. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that lycorine acts on GBM by multiple pathways, including inducing apoptosis and reactive oxygen species production. The molecular docking results showed that lycorine had strong binding efficiency with the 10 key genes. In addition, we found that the use of lycorine-induced apoptosis in U-87 MG glioblastoma cells. Here, the mechanism of action of lycorine against GBM was elucidated and verified by experiments, which provided evidence support for its clinical application.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.