大麻二酚对结肠癌抑制作用的网络药理学研究

The Inhibitory Effect of Cannabidiol on Colon Cancer based on Network Pharmacology

目的:利用网络药理学方法探索大麻二酚(CBD)抗结肠癌的分子作用机制。方法:使用DRUGBANK数据库检索CBD的作用靶点和GENECARDS数据库检索结肠癌的相关基因,并用VENNY 2.1绘制Venn图;使用STRING数据库检索目标基因所编码蛋白质之间的相互作用关系,使用Cytoscape构建药物-靶点-疾病网络和PPI,并通过Cytohubba中的MCC算法筛选出Hub gene;使用ClueGO进行GO与KEGG Pathway富集分析。结果:网络药理分析显示,CBD可与42个结肠癌相关靶蛋白相互作用。CBD可作用于CYPs、GSR、GPX、TRPx等关键靶蛋白,参与调控细胞色素P450酶功能,调控谷胱甘肽的代谢、调节类固醇激素生物合成、调控瞬时受体电位通道等多种生理途径。结论:CBD可通过调节致癌物代谢、抗氧化应激、抗炎、调节钙离子浓度等途径发挥多靶点、多通路的协同抗结肠癌作用。

Objective: To explore the molecular mechanism of cannabidiol(CBD) on colon cancer based on network pharmacology. Methods: Two databases Drug Bank and Gene Cards were used to search the target of CBD and the genes related to colon cancer. A Venn diagram was created using VENNY 2.1, and protein interactions encoded by target genes were retrieved in the STRING database. We used Cytoscape to structure the drug-target-disease network and PPI and applied Cytohubba to screen hub gene using MCC algorithm. GO and KEGG Pathway enrichment analysis were conducted using ClueGO. Results: Network pharmacology analysis showed that CBD could interact with 42 colon cancer-related target proteins. CBD acts on key target proteins, such as CYPx, GSR, GPX and TRPx, and participates in the regulation of physiological pathways including cytochrome P450 enzyme function, glutathione metabolism, steroid hormone biosynthesis, and transient receptor potential channel. Conclusion: The multitarget and multi-pathway synergism of CBD could have anti-colon-cancer effects through multiple mechanisms.