Banxia Xiexin Decoction inhibits chemoresistance in gastric cancer by regulating BMSC-derived exosome-mediated G3BP1-YWHAZ protein interaction.

OBJECTIVE: To investigate whether Banxia Xiexin Decoction (BXD) reverses bone marrow mesenchymal stem cell (BMSC)-derived exosome-induced oxaliplatin resistance in gastric cancer (GC) and to elucidate the underlying mechanism. METHODS: Oxaliplatin-resistant HGC-27 cells and human BMSCs were cultured in vitro. Exosomes were isolated and characterized by transmission electron microscopy and marker analysis. Cell viability was assessed using CCK-8 assays. Apoptosis, multidrug resistance proteins (MDR, MRP, LRP), stress granule (SG) formation, and G3BP1-YWHAZ interaction were examined by flow cytometry, immunofluorescence, Western blotting, and co-immunoprecipitation. A nude mouse xenograft model was used to evaluate in vivo effects. RESULTS: BMSC-derived exosomes enhanced oxaliplatin resistance in HGC-27 cells, reduced apoptosis, upregulated MDR-related proteins, promoted SG formation, and strengthened G3BP1-YWHAZ interaction. BXD-containing serum reversed these effects by restoring apoptosis, increasing Bax and cleaved caspase expression, suppressing resistance-associated proteins and SG assembly, and disrupting G3BP1-YWHAZ binding. In vivo, BXD attenuated exosome-mediated chemoresistance, inhibited tumor growth, and enhanced oxaliplatin-induced apoptosis. CONCLUSION: BMSC-derived exosomes promote oxaliplatin resistance in GC through activation of the G3BP1-YWHAZ axis. BXD restores chemosensitivity by interfering with this exosome-mediated pathway, supporting its use as a potential adjuvant strategy to overcome chemotherapy resistance.