Comprehensive analysis of galectin-3 inhibitors GB1107 and pimasertib targeting EMT and cancer stemness pathways to suppress hepatocellular carcinoma progression

Galectin-3 (LGALS3), a β-galactoside-binding lectin, plays a pivotal role in regulating physiological and pathological processes in hepatocellular carcinoma (HCC). This study integrates multi-omics analytics and structure-based drug screening to evaluate Galectin-3 inhibitors for HCC treatment. Transcriptomic data and immunohistochemistry confirmed elevated Galectin-3 expression in HCC tissues, with Kaplan-Meier analysis showing its association with poor survival. Single-cell RNA sequencing revealed Galectin-3’s role in immune regulation, cancer stemness, and epithelial-mesenchymal transition. Structure-based screening identified 68 compounds with significant interactions with key Galectin-3 binding sites. Molecular dynamics simulations confirmed stable complex formation between Galectin-3 and inhibitors GB1107 and Pimasertib. In vitro assays demonstrated both compounds significantly inhibited HCC cell viability, colony formation, and migration dose-dependently. GB1107 exhibited stronger cytotoxicity at lower doses, while Pimasertib induced greater apoptosis at higher concentrations. Both compounds effectively downregulated stemness and epithelial-mesenchymal transition markers. These findings suggest Galectin-3 inhibition by GB1107 and Pimasertib disrupts oncogenic pathways, reducing tumor growth and metastatic potential, and offering promising therapeutic strategies for HCC management.