| 戴雅兰,冯建国,戴五敏.基于网络药理学和生物信息学探究鹅儿猫爪汤治疗胃癌的潜在机制[J].肿瘤学杂志,2023,29(6):479-488. |
| 基于网络药理学和生物信息学探究鹅儿猫爪汤治疗胃癌的潜在机制 |
| Exploring Mechanism of Chinese Medicine EerMaozhao Decoction Against Gastric Cancer Based on Network Pharmacology and Molecular Docking |
| 投稿时间：2023-02-24 |
| DOI：10.11735/j.issn.1671-170X.2023.06.B006 |
|
 |
| 中文关键词: 鹅儿猫爪汤 胃肿瘤 网络药理学 免疫细胞浸润 分子对接 |
| 英文关键词:EerMaozhao Decoction gastric cancer network pharmacology immune cell infiltration molecular docking |
| 基金项目: |
|
| 摘要点击次数: 476 |
| 全文下载次数: 177 |
| 中文摘要: |
| 摘 要：［目的］ 通过网络药理学和分子对接技术探究鹅儿猫爪汤治疗胃癌的主要活性成分和潜在作用机制。［方法］ 通过SymMap及PubChem获取和鉴定鹅儿猫爪汤中的活性成分；借助TSCMP及pkCSM查询各活性成分的口服利用度、类药性、肠道吸收及毒性等筛选获得合适的活性成分；利用SwissTargetPrediction、Similarity ensemble approach、PharmMapper及SuperPred数据库获得活性成分的潜在作用靶点；运用Digsee、Digsnet、GeneCards及GEPIA等数据库检索胃癌相关靶点，并利用韦恩在线分析工具将药物靶点和疾病靶点取交集；根据筛选出来的药物与疾病交集靶点，借助KOBAS数据库对交集靶点进行GO功能富集和KEGG通路分析；利用STRING和Cytoscape软件构建交集靶点的蛋白相互作用（PPI）网络，依据节点度值和介值筛选出核心靶点；Kaplan-Meier plotter分析核心靶点在胃癌中的预后价值，CAMOIP分析有预后意义核心靶点与免疫细胞浸润的相关性，并经TIMMER验证；采用SwissDock等对部分活性成分与潜在靶点进行分子对接验证。［结果］ 共筛选出鹅儿猫爪汤10种活性成分，涉及304个胃癌靶点，以及参与P53、缺氧诱导因子1和细胞衰老等信号通路共222个相关信号通路。PPI及活性成分—靶点网络共筛选出2个具有预后意义的核心靶点（ERBB2和CREBBP）及对应的核心活性成分（异二氢风藤奎醇、蛇菰宁和川陈皮素）。网络分析结果表明鹅儿猫爪汤中核心活性成分可能通过作用于ERBB2和CREBBP等关键靶点调节胃癌免疫微环境，发挥抗胃癌作用。分子对接结果验证了ERBB2与异二氢风藤奎醇和蛇菰宁、CREBBP与川陈皮素结合活性较好。［结论］ 鹅儿猫爪汤通过多成分、多靶点、多通路协同作用控制胃癌的发生及进展，为今后临床进一步探讨鹅儿猫爪汤治疗胃癌的机制提供理论依据。 |
| 英文摘要: |
| Abstract：［Objective］ To explore the main active components and underlying mechanisms of Chinese medicine EerMaozhao Decoction in the treatment of gastric cancer(GC) through network pharmacology and molecular docking. ［Methods］ The active components of EerMaozhao Decoction were obtained and identified by SymMap and PubChem. The oral bioavailability， drug-likeness， intestinal absorption and minnow toxicity of each active component were investigated by TSCMP and pkCSM. And their potential targets were obtained from SwissTargetPrediction， Similarity ensemble approach， PharmMapper and SuperPred. The GC-related targets were retrieved from Digsee， Digsnet， GeneCards and GEPIA. The common targets of the drug and the disease were screened out by Venn diagram. GO and KEGG enrichment analyses of potential therapeutic targets were conducted with KOBAS database. STRING and Cytoscape were used to construct an “active component-target-protein-protein” network， and the hub targets were screened out according to the node degree and betweenness. Kaplan-Meier plotter were used to analyze the prognostic value of hub targets in GC， and the correlation between hub targets and immune cell infiltration was analyzed by COMIP and verified by TIMMER. Molecular docking was used to determine the binding activity of hub active components to key targets by SwissDock.［Results］ Network pharmacology results showed that 10 active components were screened out， involving 304 targets and 222 signal pathways(including P53， HIF-1 and cellular senescence). Two hub targets(ERBB2 and CREBBP) with prognostic significance were identified by PPI and the active ingredients-target network， as well as the corresponding hub active components of isodihydrofutoquinol A， balanophonin and nobiletin. The results of network analysis indicated that the hub active ingredients in EerMaozhao Decoction may regulate the immune microenvironment of GC by acting on the hub targets to play an anti-cancer role. The molecular docking results showed that ERBB2 had good binding activity with isodihydrofutoquinol A and balanophonin， and CREBBP had good binding activity with nobiletin. ［Conclusion］ This study shows that EerMaozhao Decoction has the characteristics of multi-component， multi-target， and multi-pathway synergistic effect in the treatment of GC， which provides a theoretical basis for in-depth research on the material basis， mechanism， and clinical application. |
|
在线阅读
查看全文 查看/发表评论 下载PDF阅读器 |