目的 基于网络药理学和分子对接探讨美洲大蠊CII-3治疗结直肠癌的作用机制。方法 通过查阅文献归纳总结筛选美洲大蠊CII-3的有效活性成分；利用PubChem数据库、SwissADME、SwissTargetPrediction平台进行作用靶点的预测；通过DisGeNet、GeneCards、TTD、OMIM数据库检索、归纳、筛选结直肠癌相关靶点；通过Venny 2.1.0对美洲大蠊CII-3活性成分作用靶点与结直肠癌相关靶点取交集，共同靶点即为CII-3抗结直肠癌的潜在作用靶点。将潜在靶点导入STRING数据库，构建蛋白互作（PPI）网络。通过PPI网络和Cytoscape 3.10.1软件及centiscape 2.2插件，筛选出美洲大蠊CII-3治疗结直肠癌的关键活性成分及核心靶点，构建“药物-成分-靶点基因”和“疾病-通路-靶点-成分-药物”网络。利用DAVID数据库对CII-3和结直肠癌潜在的作用靶点进行基因本体论（GO）功能及京都基因与基因组百科全书（KEGG）通路富集分析。利用AutoDockTools 1.5.7软件对关键活性成分与核心靶点进行分子对接验证。结果 筛选汇总了24种美洲大蠊CII-3的有效成分，通过网络药理学验证环(脯氨酸-亮氨酸)、环(亮氨酸-丙氨酸)等为主要活性成分，通过Venny 2.1.0平台取交集，得到150个潜在的作用靶点。甘油醛-3-磷酸脱氢酶（GAPDH）、蛋白激酶B1（Akt1）和表皮生长因子受体（EGFR）等为主要的核心靶点。KEGG通路富集分析显示主要涉及癌症通路、磷脂酰肌醇3-激酶（PI3K）-Akt信号通路等；分子对接显示，美洲大蠊CII-3的主要活性成分与预测的核心靶点对接结果均小于0 kJ/mol，结果显示较好的结合活性。结论 美洲大蠊CII-3可能通过多成分、多靶点、多通路协同作用治疗结直肠癌，为揭示CII-3治疗结直肠癌的分子机制提供了理论基础。

Objective To explore the anti-tumor mechanism of the Periplaneta americana peptide CII-3 based on literature summarization, network pharmacology, and molecular docking. Methods The effective active components of CII-3 were screened through literature summarization. The PubChem database, SwissADME, and SwissTargetPrediction platforms were utilized for target prediction. Relevant targets for colorectal cancer were retrieved, summarized, and screened via the DisGeNet, GeneCards, TTD, and OMIM databases. The Venny 2.1.0 was used to intersect the active components’ targets of CII-3 with colorectal cancer targets, identifying potential targets for CII-3’s action against colorectal cancer. These potential targets were imported into the STRING database to construct a protein-protein interaction (PPI) network. Using the PPI network, Cytoscape 3.10.1 software, and centiscape 2.2 plugin, key active components and core targets of CII-3 in treating colorectal cancer were screened, leading to the construction of the “drug-component-target gene” and “disease-pathway-target-component-drug” networks. The DAVID database was employed to perform GO function and KEGG pathway enrichment analyses on the potential targets of CII-3 and colorectal cancer. Molecular docking validation of the key active components and core targets was conducted using the AutoDockTools 1.5.7 software. Results A total of 24 effective components of CII-3 were summarized, with cyclo-(Pro-Leu), cyclo-(Leu-Ala), and others identified as main active components through network pharmacology validation. The Venny 2.1.0 platform yielded 150 potential targets. Major core targets included glyceraldehyde-3-phosphate dehydrogenase (GAPDH), protein kinase B1 (Akt1), and epidermal growth factor receptor (EGFR). KEGG pathway enrichment analysis indicated involvement in cancer pathways, the phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway, among others. Molecular docking revealed that the main active components of CII-3 had docking results with predicted core targets all below 0 kJ/mol, indicating good binding activity. Conclusion CII-3 may treat colorectal cancer through synergistic action involving multiple components, targets, and pathways, laying a theoretical foundation for elucidating the molecular mechanism of CII-3 in treating colorectal cancer.

R914

国家自然科学基金项目（81360319）；云南省中药饮片产业发展专项资金（2019-YG-067）