Mechanism of dendrophenol in the treatment of hepatocellular carcinoma based on network pharmacology， bioinformatics analysis and experimental validation dataset

PPI network analysis highlighted six hub targets: proto-oncogene tyrosine-protein kinase Src (SRC), erb-b2 receptor tyrosine kinase 2 (ERBB2), epidermal growth factor receptor (EGFR), AKT serine/threonine kinase 1 (AKT1), protein tyrosine phosphatase non-receptor type 11 (PTPN11), and heat shock protein 90 alpha family class A member 1 (HSP90AA1). Molecular docking suggested strong binding affinities between DEN and all six hub targets.

Bioinformatics analyses showed that HSP90AA1, AKT1, and SRC were significantly overexpressed at both the mRNA and protein levels in HCC tissues, and their high expression was significantly associated with poor prognosis.In vitro experiments demonstrated that DEN reduced the viability of HepG2 and Hep3B cells and significantly induced apoptosis. Western blot analysis showed that DEN upregulated BCL-2 associated X protein (BAX) and cleaved Caspase-3, while downregulating B-cell lymphoma 2 (BCL-2).

DEN also inhibited the phosphorylation of PI3K and AKT. Furthermore, the PI3K/AKT pathway activator Recilisib reversed the pro-apoptotic effects of DEN, indicating that the PI3K/AKT signaling pathway mediates the anti-HCC activity of DEN.Collectively, this study provides preliminary evidence that DEN exerts anti-HCC effects, potentially through modulation of the PI3K/AKT signaling pathway, regulation of BCL-2 family proteins and the caspase cascade, thereby inducing apoptosis in HCC cells and producing antitumor activity.