二至丸抑制皮肤黑素瘤细胞生长的分子网络机制及关键靶点探讨

Molecular network mechanism and key targets of Erzhi Pills inhibiting the growth of melanoma cells

关键词:  网络药理学  二至丸  皮肤黑素瘤  靶点  分子网络机制

Key words:  network pharmacology  Erzhi Pills  skin cutaneous melanoma  targets  molecular network mechanism

摘要:

[目的] 基于网络药理学探讨二至丸抑制皮肤黑素瘤生长的分子网络机制及关键靶点。[方法] 通过中药系统药理学数据库与分析平台筛选二至丸有效成分，在GEO数据库获得皮肤黑素瘤细胞与黑素细胞的差异基因表达，应用CytoScape3.7.2软件建立蛋白互作网络，利用基因表达谱交互分析数据库筛选黑素瘤枢纽基因，并进行生存分析。通过DAVID生物信息学资源进行差异基因的富集分析，并构建KEGG网络。[结果] 获得二至丸有效成分21种和皮肤黑素瘤相关靶点1889个。枢纽基因中首位是NFKBIA，它在各期皮肤黑素瘤中均呈低表达，并显著影响生存周期。代谢途径包括TNF信号通路、IL-17信号通路，趋化因子信号通路等。[结论] 二至丸通过上调NFKBIA对皮肤黑素瘤产生抑制作用，最重要的信号通路是TNF信号通路。

Abstract:

[Objective] To explore the molecular network mechanism and key targets of Erzhi Pills in inhibiting the growth of skin cutaneous melanoma based on network pharmacology.[Methods] The effective components of Erzhi Pills were screened through pharmacology database of traditional Chinese medicine system. The differential genes expression of melanoma cells and melanocytes was obtained in GEO database. The protein-protein interaction network was established by using the software of CytoScape 3.7.2,the melanoma pivotal genes was screened by using GEPIA and survival analysis was carried out. Through the enrichment and analysis of different genes in DAVID bioinformatics resources,the KEGG network was constructed.[Results] Twenty one kinds of Erzhi Pills effective components and 1889 skin cutaneous melanoma related targets were obtained. NFKBIA,the first key genes,which has a lower expression in every stage of skin cutaneous melanoma and significantly makes an impact on the survival time negatively. Metabolic pathways include TNF signaling pathway,IL-17 signaling pathway,Chemokine signaling pathway,etc.[Conclusion] Erzhi Pills can inhibit skin cutaneous melanoma by up regulating NFKBIA,and TNF signaling pathway is the most important signaling pathway.