Exploring the Potential Molecular Mechanisms of Berberine against Gastric Cancer Liver Metastasis Based on Network Pharmacology and Bioinformatics

INTRODUCTION: Gastric cancer (GC) is a common malignancy with a tendency for liver metastasis, leading to poor prognosis. Berberine (BBR), derived from Coptis chinensis Franch., exhibits potent anticancer effects on GC. However, the mechanism by which BBR affects gastric cancer liver metastasis (GCLM) remains unclear. This study employed network pharmacology and bioinformatics approaches to investigate the potential targets and molecular mechanisms of BBR as a candidate therapeutic drug for GCLM. METHODS: The targets of GCLM and BBR were acquired from public databases. Subsequently, the Protein-Protein Interaction (PPI) network and enrichment analyses were conducted to identify key targets and underlying mechanisms. Pivotal target genes were screened using machine learning algorithms. CIBERSORT analysis was applied to explore the involvement of immune cells in GCLM samples and their correlation with pivotal genes. Ultimately, molecular docking was performed to evaluate the binding affinities between BBR and pivotal target proteins. RESULTS: A total of 120 common targets were obtained after screening. These targets were primarily enriched in the PI3K/Akt signaling pathway. By employing a PPI network, the top 16 targets were acquired. Subsequently, three pivotal target genes (CCL2, SPP1, and ALB) were further identified using machine learning models. CIBERSORT analysis demonstrated significant correlations between three pivotal genes and the tumor immune microenvironment in GCLM patients, especially in the regulation of M0/M2 macrophage infiltration and dendritic cell activation. Molecular docking confirmed stable binding affinities between three pivotal target proteins and BBR. DISCUSSION: This study suggests that BBR may inhibit GCLM by targeting pivotal genes CCL2, SPP1, and ALB, blocking the PI3K/Akt pathway and remodeling the immunosuppressive microenvironment. However, further experimental validation is required to confirm these findings. CONCLUSION: This study revealed the molecular mechanism behind GCLM suppression and identified BBR as a promising therapeutic candidate, providing a basis for the development of novel treatment strategies for GCLM.