基于网络药理学和分子对接的文殊兰抗肿瘤作用机制研究

目的运用网络药理学筛选文殊兰的主要活性成分及其靶点,探究文殊兰抗肿瘤的潜在作用机制。方法通过TCMID数据库检索文殊兰的化学成分,再经Batman与Swisstargets并结合相关文献筛选出文殊兰的主要活性成分及其潜在靶点,建立靶点数据;通过Gene Cards、NCBI数据库筛选出肿瘤相关靶点;用Cytoscape3.6.3软件构建"文殊兰-成分-肿瘤-靶点"网络可视化关系图;以蛋白互作网络分析数据库,确立文殊兰和肿瘤的蛋白互作网络;利用基因本体论(gene ontology,GO)和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)数据库对相关靶点进行富集分析,了解文殊兰抗肿瘤可能的生物过程及其通路;利用分子对接进行半柔性对接反向验证。结果从文殊兰中筛选出15种活性成分,与肿瘤有关的通路有25个,文殊兰抗肿瘤主要作用于INS、GAPDH、VEGFA、EGFR、TNF等靶蛋白,KEGG通路富集结果显示,文殊兰主要作用于prostate cancer、proteoglycans in cancer、microRNAs in cancer、viral carcinogenesis等信号通路。结论文殊兰可能对前列腺癌、非小细胞癌、胰腺癌、膀胱癌、乳腺癌等具有一定的治疗作用,诱导肿瘤细胞凋亡是文殊兰成分抗肿瘤的一个重要机制。初步推测并验证了文殊兰抗肿瘤的主要靶基因和通路,为后续进一步探讨文殊兰靶向抑制肿瘤细胞提供新思路。

Antitumor mechanism of Crinum asiaticum based on network pharmacology and molecular docking

Objective To screen the main active ingredients and targets of Crinum asiaticum by using network pharmacology and explore the potential mechanism of its anti-tumor action. Method TCMID database was used to retrieve the chemical constituents of C. asiaticum, and through Batman and Swisstargets combined with related literature, the main active components and potential targets were screened out to establish target data. The tumor-related targets were screened through GeneCards database and NCBI database. The "C. asiaticum-ingredient-tumor-target" correlation network visualization diagram was constructed by Cytoscape 3.6.3 software. Protein interaction network between C. asiaticum and tumor established through analysis database by protein interaction network. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) database were adopted to analyze the gene ontology enrichment of related targets and important pathways so as to learn the possible biological processes and pathways. The molecular docking was used to conduct reverse verification of semi-flexible docking. Results A total of 15 active ingredients and 25 tumor-related pathways, of which INS, GAPDH, VEGFA, EGFR, TNF, and other target proteins were found. KEGG pathway enrichment results showed that C. asiaticum mainly acted on prostate cancer, proteoglycans in cancer, microRNAs in cancer, viral carcinogenesis via signaling pathways. Conclusion C. asiaticum may have certain therapeutic effects on prostate cancer, non-small cell carcinoma, pancreatic cancer, bladder cancer, and breast cancer by apoptotic mechanism. This study preliminarily speculated and verified the main target genes and pathways of antitumor activity of C. asiaticum, which provides a new idea for further study of the inhibition of tumor cells targeted by C. asiaticum.