基于网络药理学技术探讨长春花治疗癌症的作用机制

doi:10.5246/jcps.2023.11.073

摘要/Abstract

摘要：

基于中药分子机理的生物信息学分析工具(bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine, BATMAN-TCM)研究长春花治疗癌症的分子机制。应用BATMAN-TCM平台, 预测长春花的潜在作用靶点, 使用GeneCards数据库检索癌症靶点。然后利用Cytoscape 3.7.0软件构建化合物-疾病-靶点相互作用网络。针对长春花的抗癌靶点, 进行了基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路分析, 以确定长春花抗癌的基因功能。最后, 从长春花中筛选出9种活性成分, 构建了化合物-疾病-靶点网络。基于STRING建立的长春花靶点的PPI网络包括55个节点和328个相互作用关系。关键节点包括CTNNB1、JUN、VEGFA、ESR1、HIF1A、FOS、MTOR。此外, GO富集分析共确定了73个通路, 包括RNA聚合酶II特异性DNA结合转录因子结合、DNA结合转录因素结合、泛素蛋白连接酶结合、泛蛋白样蛋白连接酶类结合。此外, 在KEGG通路富集分析中, 获得了106条信号通路, 其中PI3K-Akt信号通路和HIF-1信号通路是与癌症相关的关键通路。本研究发现长春花通过多组分-多靶点-多途径的协同调控实现了抗癌作用, 为长春花的应用提供了理论依据和科学依据。

关键词: 长春花, 网络药理学, 活性化合物, 癌症

Abstract:

In the present study, the bioinformatics analysis tool BATMAN-TCM was employed to explore the molecular mechanism of action of Catharanthus roseus (C. roseus) in cancer treatment. The potential targets of C. roseus were predicted using BATMAN-TCM, and the GeneCards database was utilized to identify cancer-related targets. A compound-disease-target interaction network was constructed using Cytoscape 3.7.0 software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to determine the gene functions of C. roseus in counteracting cancer. Nine types of active ingredients were identified from C. roseus, and a compound-disease-target network was established. The protein-protein interaction (PPI) network of C. roseus targets was constructed using the STRING database, comprising 55 nodes and 328 interaction relationships. Key nodes in the network included CTNNB1, JUN, VEGFA, ESR1, HIF1A, FOS, and MTOR. GO analysis identified 73 items, such as RNA polymerase II-specific DNA-binding transcription factor binding, DNA-binding transcription factor binding, ubiquitin protein ligase binding, and ubiquitin-like protein ligase binding. In the KEGG pathway enrichment analysis, 106 signaling pathways were identified, with the PI3K-Akt signaling pathway and HIF-1 signaling pathway emerging as key pathways related to cancer. Overall, the research demonstrated that C. roseus exerted its anticancer effects through the synergistic regulation of multiple components, targets, and pathways. These findings provided a theoretical and scientific basis for the application of C. roseus in cancer treatment.

Key words: C. roseus, Network pharmacology, Active compounds, Cancer

Supporting:

张玉倩, 牛海英, 靳怡然. 基于网络药理学技术探讨长春花治疗癌症的作用机制[J]. 中国药学(英文版), 2023, 32(11): 911-922.

Yuqian Zhang, Haiying Niu, Yiran Jin. Network pharmacology-based strategy to investigate anticancer mechanisms of Catharanthus roseus (L.) G. Don[J]. Journal of Chinese Pharmaceutical Sciences, 2023, 32(11): 911-922.

图/表 7

Figure 1. Venn diagram of disease and drug targets.

Table 1. Nine active compounds in C. roseus.

Figure 2. C. roseus (Changchunhua)-compound-targets-cancer network map.

Figure 3. PPI network diagram of key targets.

Figure 4. GO enrichment analysis of anticancer targets (Fig. 4A and 4B are the barplot and dotplot, respectively).

Figure 5. KEGG enrichment analysis of anticancer targets (Fig. 5A and 5B are the barplot and dotplot, respectively).

Figure 6. C. roseus pathway and therapeutic modules. Three pathways constitute the compressed C. roseus pathway.

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