Exploring the anti-lung cancer mechanism of the quercetin in Tetrastigma hemsleyanum Diels & Gilg: network pharmacology, molecular docking, molecular dynamics simulation, and experimental analysis.

[ETHNOPHARMACOLOGICAL RELEVANCE] Lung cancer is not only the most widespread cancer across the globe but also the primary driver of cancer fatalities. Tetrastigma hemsleyanum Diels & Gilg (SYQ) is a rare and endemic plant in China. It exhibits pharmacological properties including wind-dispelling and phlegm-resolving, heat-clearing and detoxifying, anti-inflammatory and anti-tumor effects.

[AIM OF THE STUDY] The components with anti-lung cancer effect were isolated from SYQ, and their anti-lung cancer effect and mechanism were explored through network pharmacology, molecular dynamics simulation and in vitro cell experiments.

[MATERIALS AND METHODS] Identify the component targets of SYQ through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), GeneCards, Therapeutic Target Database (TTD), and OMIN databases, and intersect them with disease targets. The mechanism of SYQ in the treatment of non-small cell lung cancer (NSCLC) was explored by protein-protein interaction network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Study the interaction forces between the main ingredients and their corresponding targets through molecular docking and molecular dynamics simulation. Finally, the anti-tumor effect of the core component quercetin was verified by in vitro experiments.

[RESULTS] There were 132 intersection targets between SYQ components and disease targets. Potential targets for SYQ in the therapy of lung cancer include TP53, AKT1, CASP3, TNF, IL6, BCL2, and JUN. Qu can inhibit the PI3K/AKT pathway, downregulate BCL2 expression, and activate the cleavage of the apoptotic protein caspase-3, ultimately triggering apoptosis in H1299 cells.

[CONCLUSIONS] Compound Qu in SYQ can effectively inhibit the PI3K/AKT pathway, regulate the expression levels of BCL2 and CASP3 proteins, and induce apoptosis.