Elucidating the molecular mechanism of Bazhen decoction in the treatment of liver cancer: an integrated approach using network pharmacology, cancer databases, molecular docking, and experimental validation

OBJECTIVES: To investigate the Bazhen decoction (BZD) mechanism in the treatment of liver cancer (LC). METHODS: Integrative approach combining network pharmacology, HPLC, molecular docking, public cancer databases, and MTT colorimetric assay to elucidate the pharmacological mechanisms of BZD against LC. KEY FINDINGS: We identified 647 common targets between BZD and LC, with PPI analysis revealing SRC, PIK3CA, AKT1, HSP90AA1, and STAT3 as core targets. KEGG pathway analysis further highlighted PI3K-AKT, MAPK, HIF-1, and Rap1 signaling pathways as critical mechanisms mediating BZD's therapeutic effects. Notably, validation using cancer databases showed that many core targets exhibit differential messenger RNA (mRNA) and protein expression between LC and normal tissues, with their expression levels significantly associated with the overall survival of LC patients. Molecular docking analysis revealed strong binding affinities between the majority of core compounds and their corresponding core targets. HPLC analysis was performed using neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, ferulic acid, and senkyunolide I as reference standards. MTT assays confirmed that BZD significantly inhibited the proliferation of HepG2 and Huh7 cells in a time- and dose-dependent manner. CONCLUSIONS: BZD exerts anti-LC effects through multi-target regulation, particularly involving AKT1, PIK3CA, SRC, and HSP90AA1, as well as suppression of the PI3K-AKT signaling pathway. These findings provide a mechanistic basis for its potential clinical application in LC therapy and warrant further in vivo investigation.