Multi-omics analysis reveals psoralen to suppresses renal cell carcinoma through the PI3K/AKT pathway

Psoralen (PSO) is the active component of Trigonostemon xyphophyllorides (TX) and exhibits therapeutic potential against renal cell carcinoma (RCC). Despite this, there is a lack of research investigating the therapeutic efficacy of PSO specifically on RCC. In the present study, an integrated multi-omics strategy was employed to systematically evaluate the anti-RCC effects of PSO. PSO was subjected to network pharmacology analysis, identifying 78 RCC-related target genes. Pathway enrichment analysis suggested the involvement of the PI3K/AKT signaling pathway as a key regulatory mechanism. Molecular docking analysis and molecular dynamics simulations indicated a strong binding affinity and enhanced structural stability of the bound complexes between PIK3CA (PDB ID: 9B4T) and PSO. In vitro experiments demonstrated a potent antiproliferative effect of PSO on multiple RCC cell lines, with the strongest inhibition observed in ACHN cells (IC₅₀ = 1.74±0.90 µM), By contrast, minimal cytotoxicity was observed towards the non-cancerous renal epithelial cell line HK-2 at concentrations ≤8 µM. Furthermore, PSO treatment resulted in the significant downregulation of the PI3K-AKT signaling pathway-related genes, which was supported by results from transcriptomic analysis identifying 593 differentially expressed genes. The present findings offer quantitative and mechanistic evidence supporting the clinical utilization of TX in the treatment of RCC, thereby advancing its further research and development.