Abstract

Non-small-cell lung cancer (NSCLC) accounts for approximately 80% of lung cancer cases, which is a leading cause of cancer mortality worldwide. While therapies such as chemotherapy, radiation, immunotherapy and targeted drugs have shown efficacy, resistance remains a major obstacle. Traditional Chinese medicine (TCM) offers a multi-target approach that may help overcome resistance. This study analyzed the active ingredients of Huangqi and Danggui decoction (HQDGD), a classic TCM formula, and their effects on NSCLC using network pharmacology and experimental validation. Active compounds were identified from TCM databases and linked to gene targets using prediction tools and were compared to NSCLC-related genes to find shared targets. Protein-protein interaction network analysis and pathway enrichment analysis were used to find HQDGDs pharmacology and experiments on lung cancer A549 cells validated that key HQDGD compounds curcumin, quercetin and -angelicalactone inhibited proliferation and migration, suppressed JAK2/STAT3 activation, and downregulated downstream HIF1A and VEGF. The multi-target actions of HQDGD may overcome resistance in NSCLC. Our integrated computational and experimental approach elucidated the compound-target-pathway mechanisms of a TCM formula against NSCLC, supporting future drug development and research.

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