Ginkgetin inhibits non-small cell lung cancer via the HSP90-AKT signaling pathway.

Lung cancer (LC) represents a pivotal cause of human mortality. Ginkgetin (GK), a bioactive flavonoid derived from Ginkgo biloba leaves, exhibits anti-tumor properties. Our objective was to integrate network pharmacology with cellular experiments to elucidate the potential targets and molecular mechanisms of GK in non-small cell lung cancer (NSCLC) therapy. We systematically extracted data from multiple databases to identify potential therapeutic targets and pathways for GK against NSCLC. Then, cellular experiments were conducted to verify GK's inhibitory effect on A549 and LLC cells. Network pharmacology identified 52 potential targets, 5 key proteins, and 113 signaling pathways. Molecular docking results showed that core proteins and GK can bind tightly. The MD simulation revealed that EGFR exhibits strong binding to GK. Differential gene expression analysis demonstrated elevated levels of proteins such as HSP90AA1 in NSCLC. Cellular experimental methods reported that GK suppresses A549 and LLC cell proliferation and metastasis. Our findings suggest that GK may exert its anti-NSCLC effect through the HSP90-AKT signaling pathway, providing a foundation for further study.