Molecular mechanism of Acori Tatarinowii Rhizoma-Curcumae Radix in treating precancerous lesions of gastric cancer based on network pharmacology and cell experiments

A malignant transformation cell (MC) model was established by treating GES-1 cells with 1-methyl-3-nitro-1-nitrosoguanidine (N-methyl-N'-nitro-N-nitrosoguanidine, MNNG). The effect of ATR-CR on MC cell migration was evaluated by wound healing assay. mRNA expression levels of relevant genes were determined by RT-qPCR, and cell apoptosis was assessed by flow cytometry. Network pharmacology screening identified six potential active components, corresponding to 117 drug targets, while 748 PLGC-related disease targets were retrieved, yielding 43 overlapping targets between drug and disease.

GO functional enrichment analysis encompassed 339 terms across biological processes, cellular components, and molecular functions, and KEGG pathway enrichment involved 122 signaling pathways including cancer pathways and metabolic pathways. Molecular docking revealed that the core active components 8-prenylkaempferol, kaempferol, and naringenin exhibited favorable binding affinities with key targets, including phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit γ (PIK3CG), serine/threonine-protein kinase 1 (AKT1), B-cell lymphoma 2 (BCL-2), BCL-2-associated X protein (BAX), and Caspase-3 (CASP3).

Cellular experiments demonstrated that ATR-CR significantly suppressed MC cell migration, downregulated PIK3CG, AKT1 and BCL-2 mRNA expression, upregulated BAX and CASP3 mRNA expression, and effectively promoted early apoptosis in MC cells. Collectively, these findings suggested that ATR-CR may induce early apoptosis in MC cells by inhibiting aberrant activation of the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway, providing experimental evidence for its clinical application in PLGC treatment.