基于网络药理学研究灵芝干预肝癌的作用机制

A study on the action mechanism of Ganoderma lucidum on liver cancer based on network pharmacology

目的:灵芝辅助抗癌临床治疗20余年,但是其具体的活性成分及其对肿瘤的调控机制尚不明确。文章采用网络药理学的方法探究灵芝干预肝癌的作用机制,为灵芝进一步作为抗癌治疗和化学预防药物提供科学依据。方法:使用中药系统药理学数据库与分析平台数据库筛选与预测灵芝的活性成分和作用靶点,分别在GeneCards、OMIM、TTD、DrugBank和PharmGKB等5个数据库筛选、去重,获取治疗肝癌的相关靶点。利用Venny在线工具获得灵芝与肝癌的共同作用靶点(即灵芝干预肝癌的靶点);基于String数据库进行灵芝-肝癌共同靶点相互作用网络的构建与分析;使用Cytoscape软件构建灵芝干预肝癌的“活性成分-靶点”图。最后利用R软件对共同作用靶点进行基因本体论(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析。结果:经筛选与预测,获得灵芝的活性成分13个和作用靶点38个;GO和KEGG富集分析得到41个生物学过程和28条信号通路。结论:通过构建和预测药物、靶点-通路网络证实和预测了灵芝治疗肝癌的分子机制,提示有11个核心靶基因可以作为灵芝治疗肝癌的潜在标志物。

Objective: Ganoderma lucidum has assisted anti-cancer clinical treatment for more than 20 years, but its specific active ingredients and its regulatory mechanism on tumors are still unclear. The method of network pharmacology is used to explore the action mechanism of Ganoderma lucidum on liver cancer, hoping to provide scientific basis for ganoderma lucidum as a further anti-cancer treatment. Methods: TCMSP database was used to screen and predict the active ingredients and targets of ganoderma lucidum, screen and remove duplicates in 5 databases such as Gene Cards, OMIM, TTD, Drug Bank and Pharm GKB, respectively, to obtain relevant targets for the treatment of liver cancer. Venny online tool was used to obtain ganoderma lucidum Co-acting targets with liver cancer. The Ganoderma-liver cancer common target interaction network was constructed and analyzed based on the String database;cytoscape software was used to construct the “active ingredient-target” map of ganoderma lucidum on liver cancer. Finally, R software was used to to perform GO and KEGG enrichment analysis on the co-acting target. Results: After screening and prediction, a total of 13 active ingredients and 38 targets of ganoderma lucidum were obtained. GO and KEGG enrichment analysis revealed 41 biological processes and 28 signal pathways. Conclusion: This study confirmed and predicted the molecular mechanism of ganoderma lucidum in the treatment of liver cancer by constructing and predicting drugs and target-pathway networks, suggesting that 11 core target genes can be used as potential markers of ganoderma lucidum in the treatment of liver cancer.