Hou Fanfan, Liu Yang, Cheng YaHsin, Zhang Ni, Yan Wenpeng, Zhang Fang
Stomatology Hospital, Shanxi Medical University, Taiyuan 030001, China.
Department of Physiology, School of Medicine, China Medical University, Taichung, Taiwan.
Evid Based Complement Alternat Med. 2021 Jul 13;2021:5597586. doi: 10.1155/2021/5597586. eCollection 2021.
Georgi (SBG) has been widely shown to induce apoptosis and inhibit invasion and migration of various cancer cells. Increased evidence shows that SBG may be useful to treat oral squamous cell carcinoma (OSCC). However, the biological activity and possible mechanisms of SBG in the treatment of OSCC have not been fully elucidated. This study aimed to clarify the bioactive component and multitarget mechanisms of SBG against OSCC using network pharmacology and molecular docking.
Traditional Chinese Medicine Systems Pharmacology (TCMSP) database was used to predict the active components in SBG, and putative molecular targets of SBG were identified using the Swiss Target Prediction database. OSCC-related targets were screened by GeneCards, Online Mendelian Inheritance in Man (OMIM), and Therapeutic Target Database (TTD). Then, we established protein-protein interaction (PPI), compound-target-disease (C-T-D), and compound-target-pathway (C-T-P) networks by Cytoscape to identify the main components, core targets, and pharmacological pathways of SBG against OSCC via applying data mining techniques and topological parameters. Metascape database was utilized for Gene Ontology (GO) and pathway enrichment analysis. The potential interaction of the main components with core targets was revealed by molecular docking simulation, and for the correlation between core targets and OSCC prognosis analysis, the Kaplan-Meier Plotter online database was used.
There were 25 active compounds in SBG and 86 genes targeted by OSCC. A total of 141 signaling pathways were identified, and it was found that the PI3K-Akt signaling pathway may occupy core status in the anti-OSCC system. GO analysis revealed that the primary biological processes were related to apoptosis, proliferation, and migration. Molecular docking results confirmed that core targets of OSCC had a high affinity with the main compounds of SBG.
Our study demonstrated multicomponent, multitarget, and multipathway characteristics of SBG in the treatment of OSCC and provided a foundation for further drug development research.
已广泛证实Georgi（SBG）可诱导多种癌细胞凋亡，并抑制其侵袭和迁移。越来越多的证据表明，SBG可能对治疗口腔鳞状细胞癌（OSCC）有用。然而，SBG治疗OSCC的生物学活性及可能机制尚未完全阐明。本研究旨在运用网络药理学和分子对接技术阐明SBG抗OSCC的生物活性成分及多靶点作用机制。
利用中药系统药理学（TCMSP）数据库预测SBG中的活性成分，并通过瑞士靶点预测数据库鉴定SBG的潜在分子靶点。通过GeneCards、在线人类孟德尔遗传数据库（OMIM）和治疗靶点数据库（TTD）筛选OSCC相关靶点。然后，我们通过Cytoscape构建蛋白质-蛋白质相互作用（PPI）、化合物-靶点-疾病（C-T-D）和化合物-靶点-通路（C-T-P）网络，运用数据挖掘技术和拓扑参数确定SBG抗OSCC的主要成分、核心靶点和药理通路。利用Metascape数据库进行基因本体（GO）和通路富集分析。通过分子对接模拟揭示主要成分与核心靶点的潜在相互作用，对于核心靶点与OSCC预后分析的相关性，使用Kaplan-Meier Plotter在线数据库。
SBG中有25种活性化合物，OSCC靶向86个基因。共鉴定出141条信号通路，发现PI3K-Akt信号通路可能在抗OSCC系统中占据核心地位。GO分析表明，主要生物学过程与凋亡、增殖和迁移有关。分子对接结果证实，OSCC的核心靶点与SBG的主要化合物具有高亲和力。
我们的研究证明了SBG治疗OSCC具有多成分、多靶点和多通路的特点，为进一步的药物开发研究提供了基础。
