背景:复方斑茅胶囊(FFBM),中药,多年来一直被用于治疗原发性肝癌(PLC)。然而,生物活性成分,FFBM治疗PLC的机制尚不清楚。我们的目标是利用网络药理学来研究这些方面,并随后通过临床数据验证其有效性。
方法:从HERB数据库获得FFBM成分,并使用SwissTargetPrediction数据库筛选生物活性成分。PharmMapper和GEO数据库用于获取FFBM和PLC的靶标和差异表达基因(DEGs),分别。使用维恩图确定了常见目标,然后进行富集和蛋白质-蛋白质相互作用(PPI)分析。此外,利用Cytoscape软件鉴定Hub基因并构建成分靶途径网络。随后,回顾性收集2008年1月至2019年12月在我院接受肝动脉化疗栓塞(TACE)治疗的确诊为不可切除PLC的患者.最后,进行Cox分析以揭示FFBM在不可切除的PLC的治疗中的作用。
结果:FFBM有232个目标,PLC有1582个DEG。HSP90AA1和SRC被确定为关键靶标。阿尔法-桑他洛尔,甘草酸,和莫罗尼甙被确定为前三种生物活性成分。富集分析揭示了FFBM用于治疗PLC与多种途径之间的显着联系,如化学致癌作用,PI3K-AKT,Rap1,FoxO,MAPK,和VEGF途径。临床数据显示,食用FFBM可显着改善不可切除的PLC的预后,风险比为0.69。
结论:我们的研究确定了FFBM的生物活性成分及其治疗PLC的潜在机制。此外,我们通过临床数据验证了有效性.
BACKGROUND: Fufang Banmao capsules (FFBM), a traditional Chinese medicine, has been used to treat primary liver cancer (PLC) for several years. However, the bioactive ingredients, and mechanism of FFBM for treating PLC remains unclear. Our objective is to utilize network pharmacology to investigate these aspects and subsequently validate their effectiveness through clinical data.
METHODS: The FFBM ingredients were obtained from the HERB database and screened for bioactive ingredients using the SwissTargetPrediction database. The PharmMapper and GEO database were used to acquire targets and differentially expressed genes (DEGs) for FFBM and PLC, respectively. Common targets were identified using Venn diagrams, followed by enrichment and protein-protein interaction (PPI) analysis. Furthermore, the Cytoscape software was utilized to identify Hub genes and construct the ingredienttarget- pathway network. Subsequently, patients diagnosed with unresectable PLC who underwent transcatheter arterial chemoembolization (TACE) at our hospital between January 2008 and December 2019 were retrospectively collected. Finally, Cox analysis was conducted to reveal the role of FFBM in the treatment of unresectable PLC.
RESULTS: FFBM had 232 targets, and PLC had 1582 DEGs. HSP90AA1 and SRC were identified as crucial targets. Alpha-santalol, glycyrrhizin, and morroniside were identified as the top three bioactive ingredients. Enrichment analysis revealed a significant connection between FFBM utilization for treating PLC and multiple pathways, such as chemical carcinogenesis, PI3K-AKT, Rap1, FoxO, MAPK, and VEGF pathway. Clinic data revealed that consuming FFBM significantly improved the prognosis of unresectable PLC with a hazard ratio of 0.69.
CONCLUSIONS: Our study identified the bioactive ingredients of FFBM and its potential mechanisms for treating PLC. Additionally, we validated the effectiveness through clinical data.