Wu Ji, Li Xue-Yu, Liang Jing, Fang Da-Lang, Yang Zhao-Jian, Wei Jie, Chen Zhi-Jun
Department of Neurosurgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.
Department of Pediatrics, The Second Affiliated Hospital of Xinjiang Medical University, Urumchi, China.
Front Genet. 2022 Aug 15;13:940462. doi: 10.3389/fgene.2022.940462. eCollection 2022.
Glioblastoma multiforme (GBM) is the most aggressive primary nervous system brain tumor. There is still a lack of effective methods to control its progression and recurrence in clinical treatment. It is clinically found that Xiaoliu Decoction (XLD) has the effect of treating brain tumors and preventing tumor recurrence. However, its mechanism is still unclear. Search the Traditional Chinese Medicine System Pharmacology Database (TCSMP) for efficient substances for the treatment of XLD in the treatment of GBM, and target the targeted genes of the effective ingredients to construct a network. At the same time, download GBM-related gene expression data from the TCGA and GTEX databases, screen differential expression bases, and establish a drug target disease network. Through bioinformatics analysis, the target genes and shared genes of the selected Chinese medicines are analyzed. Finally, molecular docking was performed to further clarify the possibility of XLD in multiple GBMs. We screened 894 differentially expressed genes in GBM, 230 XLD active ingredients and 169 predicted targets of its active compounds, of which 19 target genes are related to the differential expression of GBM. Bioinformatics analysis shows that these targets are closely related to cell proliferation, cell cycle regulation, and DNA synthesis. Finally, through molecular docking, it was further confirmed that Tanshinone IIA, the active ingredient of XLD, was tightly bound to key proteins. To sum up, the results of this study suggest that the mechanism of XLD in the treatment of GBM involves multiple targets and signal pathways related to tumorigenesis and development. This study not only provides a new theoretical basis for the treatment of glioblastoma multiforme with traditional Chinese medicine, but also provides a new idea for the research and development of targeted drugs for the treatment of glioblastoma multiforme.
多形性胶质母细胞瘤(GBM)是最具侵袭性的原发性神经系统脑肿瘤。在临床治疗中,仍缺乏控制其进展和复发的有效方法。临床发现,消瘤汤(XLD)具有治疗脑肿瘤和预防肿瘤复发的作用。然而,其作用机制仍不清楚。在中药系统药理学数据库(TCSMP)中搜索消瘤汤治疗GBM的有效物质,并针对有效成分的靶向基因构建网络。同时,从TCGA和GTEX数据库下载GBM相关基因表达数据,筛选差异表达基因,建立药物-靶标-疾病网络。通过生物信息学分析,对所选中药的靶标基因和共享基因进行分析。最后,进行分子对接以进一步阐明消瘤汤在多种GBM中的作用可能性。我们在GBM中筛选出894个差异表达基因、230种消瘤汤活性成分及其活性化合物的169个预测靶标,其中19个靶标基因与GBM的差异表达相关。生物信息学分析表明,这些靶标与细胞增殖、细胞周期调控和DNA合成密切相关。最后,通过分子对接进一步证实,消瘤汤的活性成分丹参酮IIA与关键蛋白紧密结合。综上所述,本研究结果表明,消瘤汤治疗GBM的机制涉及多个与肿瘤发生发展相关的靶标和信号通路。本研究不仅为中医药治疗多形性胶质母细胞瘤提供了新的理论依据,也为多形性胶质母细胞瘤靶向药物的研发提供了新思路。