Abstract
Non-small cell lung cancer (NSCLC) is a leading cause of cancer mortality worldwide, necessitating new treatment approaches with minimal side effects. In the present study, the potential of Bergapten (5-methoxypsoralen), a natural furanocoumarin compound, as a therapeutic agent against NSCLC was investigated by using network pharmacology, molecular docking and in vitro validation. Bergapten targets were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and SwissTarget databases, whilst lung cancer-related targets were sourced from GeneCards and DisGeNET. Protein-protein interaction analysis and molecular docking were performed to identify key targets. The inhibitory effects of Bergapten on lung cancer cells were assessed using Cell Counting Kit-8 assays, wound healing assays, cell migration experiments, flow cytometry and western blotting. SC79 was used to verify the regulation of Bergapten on the PI3K/AKT pathway. Network pharmacology identified 51 targets, one signaling pathway and four Gene Ontology projects associated with the action of Bergapten against NSCLC. Key targets identified included glycogen synthase kinase-3β, Janus kinase 2, phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit α and protein tyrosine kinase 2. In vitro experiments demonstrated that Bergapten significantly inhibited cell viability, promoted apoptosis, induced cellular senescence and inhibited the PI3K/AKT signaling pathway in NSCLC cells. In conclusion, Bergapten exerts its anti-NSCLC effects through the PI3K/AKT pathway, promoting cell senescence and inhibiting inflammation. These findings suggest that Bergapten has potential as a therapeutic agent for NSCLC.