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Protein & Peptide Letters

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ISSN (Print): 0929-8665
ISSN (Online): 1875-5305

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Research Article

Combining Network Pharmacology, Molecular Docking and Preliminary Experiments to Explore the Mechanism of Action of FZKA Formula on Non-small Cell Lung Cancer

Author(s): Zhuixing Liu, Jie Zhang, Jinpeng Liu*, Lihong Guo, Guangwei Chen, Yu Fang and Yang Yang*

Volume 30, Issue 12, 2023

Published on: 13 November, 2023

Page: [1038 - 1047] Pages: 10

DOI: 10.2174/0109298665268153231024111622

Price: $65

Abstract

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.

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