Background: Clinically, Fuzhengkangai formulation (FZKA) has been proven to have significant therapeutic effects on non-small lung cancer (NSCLC), although the mechanism is unknown. We aimed to explore the potential mechanism of FZKA in the treatment of NSCLC in this study. Methods: We obtained the active components and targets of FZKA by TCMSP. The target genes of NSCLC were searched from OMIM, GEO (GSE18842), and GeneCards database. Cytoscape (3.7.2) software was used to construct a “drug-compound-cross-target interaction” interaction network, and the STING database was used to analyze previous cross-target interactions. Meanwhile, the results were visualized and processed by performing GO enrichment analysis and KEGG signaling pathway enrichment analysis at the target site. The core targets were docked with active components through AutoDockTools-1.5.6 software. Finally, we used cellular experiments to validate the bioinformatics predictions. Results: There were 40 active and 465 potential genes from the TCMSP database. Key active chemicals, namely Quercetin, Kaempferol, Luteolin, and Tanshinone IIA, and 176 targets were deemed as targets of FZKA against NSCLC by PPI network analysis. GO and KEGG enrichment analyses suggest that FZKA acts primarily through the PI3K-AKT and MAPK signaling pathways in the treatment of NSCLC. Moreover, cellular assays showed that Quercetin, Kaempferol, Luteolin, and Tanshinone IIA not only reduced the viability of A549 cells and promoted apoptosis but also significantly decreased the p-AKT/AKT and p-ERK1/2/ERK1/2 ratios. Conclusion: Our data suggested that FZKA can be involved in the treatment of NSCLC through multiple components, targets and pathways.

中文翻译：

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结合网络药理学、分子对接和初步实验探索FZKA方治疗非小细胞肺癌的作用机制


背景：临床证明扶正康艾方（FZKA）对非小细胞肺癌（NSCLC）具有显着的治疗效果，但其作用机制尚不清楚。本研究旨在探讨 FZKA 治疗 NSCLC 的潜在机制。方法：通过TCMSP获得FZKA的活性成分和靶点。从OMIM、GEO（GSE18842）和GeneCards数据库中搜索NSCLC的靶基因。使用Cytoscape（3.7.2）软件构建“药物-化合物-跨靶点相互作用”相互作用网络，并使用STING数据库分析先前的跨靶点相互作用。同时，通过对靶位点进行GO富集分析和KEGG信号通路富集分析，对结果进行可视化和处理。通过AutoDockTools-1.5.6软件将核心目标与有源组件对接。最后，我们使用细胞实验来验证生物信息学预测。结果：TCMSP数据库中有40个活跃基因和465个潜在基因。通过 PPI 网络分析，关键活性化学物质槲皮素、山奈酚、木犀草素和丹参酮 IIA 以及 176 个靶点被视为 FZKA 对抗 NSCLC 的靶点。 GO和KEGG富集分析表明FZKA在NSCLC治疗中主要通过PI3K-AKT和MAPK信号通路发挥作用。此外，细胞测定表明，槲皮素、山奈酚、木犀草素和丹参酮 IIA 不仅降低 A549 细胞的活力并促进细胞凋亡，而且还显着降低 p-AKT/AKT 和 p-ERK1/2/ERK1/2 比率。结论：我们的数据表明，FZKA 可以通过多个成分、靶点和途径参与 NSCLC 的治疗。