基于GEO数据库、网络药理学、分子对接和 分子动力学模拟探究陈皮治疗结直肠癌的 潜在机制

Investigation of the Potential Mechanism of Pericarpium Citri Reticulatae in the Treatment of Colorectal Cancer Based on GEO Database, Network Pharmacology, Molecular Docking and Molecular Dynamics Simulation

摘要: 目的：通过整合GEO数据库、网络药理学和分子对接技术，探究陈皮治疗结直肠癌(colorectal cancer)的潜在机制。方法：利用本草组鉴数据库平台(HERB)筛选陈皮的活性成分，根据活性成分通过SwissTargetPrediction预测靶点，从Gene Cards、OMIM、TTD、CTD和GEO数据库获取结直肠癌相关疾病靶点；利用Cytoscape 3.10.4和STRING数据库构建蛋白质互作网络并筛选核心活性成分与关键靶点；采用R-4.5.2进行基因本体(GO)和京都基因与基因组百科全书(KEGG)通路富集分析；运用CADD分子对平台进行分子对接验证。结果：共获得60个陈皮活性成分、924个对应靶点、4356个结直肠癌靶点和145个有差异的交集靶点。核心活性成分包括柚皮素、(2R)-黄烷酮和橙皮素等57种；关键靶点包括原癌基因酪氨酸激酶(SRC)、蛋白激酶B (PKB) α (AKT1)、信号转导和转录激活因子3 (STAT3)、丝裂原活化蛋白激酶1 (ERK2) (MAPK1)等10个基因。富集分析表明，这些靶点显著富集于磷脂酰肌醇3激酶–蛋白激酶B (PI3K-Akt)、低氧诱导因子-1 (HIF-1)、丝裂原活化蛋白激酶(MAPK)等信号通路。结论：研究表明，陈皮通过“多成分–多靶点–多通路”的协同机制，在抗结直肠癌中发挥潜在作用，为其后续试验验证及临床应用提供参考。

Abstract: Objective: To explore the potential mechanism of Pericarpium Citri Reticulatae (Chenpi) in the treatment of colorectal cancer by integrating the GEO database, network pharmacology and molecular docking technology. Methods: The active components of Chenpi were screened via the HERB database platform. Targets were predicted for the active components using SwissTargetPrediction. Colorectal cancer-related disease targets were retrieved from the Gene Cards, OMIM, TTD, CTD and GEO databases. The protein-protein interaction network was constructed, and core active components and key targets were screened using Cytoscape 3.10.4 and the STRING database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using R-4.5.2. Molecular docking validation was performed on the CADD molecular docking platform. Results: A total of 60 active components of Chenpi, 924 corresponding targets, 4356 colorectal cancer targets and 145 differential overlapping targets were obtained. Fifty-seven core active components were identified, including naringenin, (2R)-flavanone and hesperetin. Ten key genes were determined as critical targets, including proto-oncogene tyrosine-protein kinase (SRC), protein kinase B (PKB) α (AKT1), signal transducer and activator of transcription 3 (STAT3), and mitogen-activated protein kinase 1 (ERK2) (MAPK1). Enrichment analysis showed that these targets were significantly enriched in the phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt), hypoxia-inducible factor-1 (HIF-1) and mitogen-activated protein kinase (MAPK) signaling pathways. Conclusion: This study shows that Chenpi plays a potential role in the treatment of colorectal cancer through the synergistic mechanism of “multi-component, multi-target and multi-pathway”, and provides a reference for its further experimental verification and clinical application.