The potential of Humulus scandens in delaying non-small cell lung cancer: Targeting the PI3K/Akt signaling pathway to inhibit tumor growth and metastasis.

AIMS: Effective treatments for non-small cell lung cancer (NSCLC) remain limited, necessitating the development of new therapeutic strategies. The traditional Chinese medicine Humulus scandens exhibits antioxidant, anti-inflammatory, and antitumor activities. However, its specific effects on NSCLC growth and metastasis remain unclear and require further investigation.

METHODS: The inhibitory effects of Humulus scandens on NSCLC growth and metastasis were evaluated using mouse xenograft and lung metastasis models. Network pharmacology and transcriptomic analyses were performed to elucidate the underlying mechanisms. Molecular docking, molecular dynamics simulations, and cellular thermal shift assay were used to assess the direct targeting of phosphatidylinositol 3-kinase (PI3K) by core components. In vitro experiments in LLC cells assessed cell viability, proliferation, apoptosis, migration, and invasion. PI3K/(protein kinase B) Akt inhibitors were used to validate pathway involvement.

RESULTS: Humulus scanden inhibited NSCLC growth and metastasis in vivo, disrupted tumor architecture, suppressed proliferation, and promoted apoptosis. Integrated analyses indicated a critical role of the PI3K/Akt pathway. Molecular studies established direct binding to PI3K. In vitro, the extract reduced LLC cell viability, proliferation, migration, and invasion, and induced apoptosis. These effects were partially attenuated by PI3K/Akt inhibitors.

CONCLUSION: Humulus scanden inhibits NSCLC growth and metastasis, at least in part, through suppression of the PI3K/Akt pathway, supporting its potential as an adjuvant therapy for NSCLC.