Exploring the mechanism of Scleromitrion diffusum (Willd.) in treating lung cancer based on network pharmacology and experimental validation.

ABSTRACT

This study aims to elucidate the mechanisms by which the effective components of Scleromitrion diffusum (Willd.) (SDW) treat lung cancer, using network pharmacology, in vitro cell experiments, and molecular docking methods. Network pharmacology techniques were employed to construct a network of SDW components, lung cancer targets, and signaling pathways. A proteinprotein interaction (P P I) network was built for target genes, identifying core gene targets. Signaling pathway and biological process analyses were conducted. MT T assays measured cell viability, and Western blot analysis assessed the impact of core protein targets and key pathway proteins on the stemness of three lung cancer cell lines. Molecular docking was performed to link SDW components with core proteins and key pathway targets related to lung cancer. SDW was found to target 88 genes and 5 active components (2-methoxy-3-methyl-9-10-anthraquinone, stigmasterol, beta-sitosterol, quercetin, and poriferasterol) relevant to lung cancer treatment. The P I3K/Akt and MEK/ERK pathways were identified as major signaling pathways. Extracts from SDW roots significantly inhibited the proliferation of three lung cancer cell lines (A549, HCC827, and NCIH-1395), primarily via P I3K/Akt and MEK/ERK pathways, significantly reducing the expression of p-Akt and p-Erk1/2 and slightly inhibiting caspase-9, p-P I3K, and EGFR expression. Molecular docking confirmed the strong binding activities of SDW components with lung cancer-related core proteins and key pathway targets. SDW may regulate apoptosis and proliferation in lung cancer treatment through P I3K-Akt and MAP K/ERK signaling pathways. The combination of network pharmacology, molecular docking, and experimental validation provides valuable insights into the molecular mechanisms of SDW in lung cancer therapy.