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image of Sanguinarine Suppresses Lung Adenocarcinoma via TGF-β1/Smad3 Pathway: Insights from Network Analysis and Experimental Validation
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Abstract

Introduction

This study elucidates molecular mechanisms underlying sanguinarine (SAN)-mediated inhibition of Lung Adenocarcinoma (LUAD) progression.

Methods

A Protein-Protein Interaction (PPI) network was constructed, and core targets were visualized using Cytoscape. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed with DAVID, while Reactome, WikiPathways, and MSigDB Hallmark analyses utilized Enrichr. Core targets expression and immune infiltration in LUAD were validated using The Cancer Genome Atlas (TCGA). Molecular docking assessed binding affinity between SAN and core targets, and experiments confirmed SAN's suppression of LUAD progression the TGF-β1/Smad3 pathway.

Results

Ten core targets of SAN in LUAD were identified. GO analysis revealed biological processes including proliferation, apoptosis, and signal transduction. Significantly enriched cancer-related pathways included PI3K-Akt, MAPK, Ras, and TGF-β signaling, the latter of which was significantly enriched across KEGG, Reactome, WikiPathways, and MSigDB Hallmark analyses. Molecular docking demonstrated a strong binding affinity between SAN and core targets. , SAN suppressed proliferation and autophagy in A549 cells while promoting apoptosis by inhibiting the TGF-β1/Smad3 signaling pathway.

Discussion

The results demonstrate SAN's multi-target action against LUAD, notably through the inhibition of TGF-β1/Smad3, providing a mechanistic basis within oncogenic networks. Limitations include reliance on models and the preclinical focus. Future work requires validation and clinical translation.

Conclusion

This study identifies key targets and pathways for SAN's inhibition of LUAD progression, validating its effect through the suppression of TGF-β1/Smad3 and providing experimental evidence for clinical application in LUAD therapy.

© 2026 The Author(s). Published by Bentham Science Publishers.
This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
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2026-01-09
2026-01-27

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Sanguinarine Suppresses Lung Adenocarcinoma via TGF-β1/Smad3 Pathway: Insights from Network Analysis and Experimental Validation
Bentham Science Publishers ; https://doi.org/10.2174/0113816128404840251114063502
/content/journals/cpd/10.2174/0113816128404840251114063502
/content/journals/cpd/10.2174/0113816128404840251114063502
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  • Article Type:     Research Article
Keywords: sanguinarine ; lung adenocarcinoma ; bioinformatics ; flow cytometry ; molecular docking ; Network pharmacology

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