Abstract
OBJECTIVE: This study aimed to elucidate the molecular mechanisms by which Apigenin (APG) reverses MET-TKI resistance in non-small cell lung cancer (NSCLC). METHODS: Network pharmacology and molecular docking were used to identify potential targets and signaling pathways of APG. Functional enrichment and protein-protein interaction analyses were integrated with in vitro validation, including CCK-8, wound healing, flow cytometry, and Western blot assays. RESULTS: Key hub genes such as MET, IGF1R, and PTGS2 were identified, primarily enriched in the PI3K/AKT and MAPK pathways. APG inhibited cell proliferation and migration, enhanced apoptosis, and reduced phosphorylation of MET and AKT in MET-TKI-resistant EBC-1-TepR cells. CONCLUSION: This study provides systematic evidence by integrating computational approaches with experimental methods, revealing that APG can regulate multiple targets related to drug resistance and inhibit the MET/PI3K/AKT signaling pathway. This indicates that APG can reverse acquired MET-TKI resistance in non-small cell lung cancer by targeting the core recovery pathways within the tumor. It offers a novel combination strategy for adjuvant treatment to overcome MET-TKI resistance in NSCLC.