Molecular mechanism by which dichotomitin inhibits growth and metastasis of gastric cancer MKN-45 cells via the EGFR/ROS signaling pathway.
TL;DR
Dichotomitin inhibited proliferation, induced cell cycle arrest and apoptosis, and suppressed migration in GC cells by modulating EGFR-related ROS-dependent signaling pathways.
Abstract
INTRODUCTION Dichotomitin (DC), an isoflavone from Belamcanda chinensis, has anti-inflammatory and antioxidant properties, but its role in gastric cancer (GC) remains unexplored. This study aimed to elucidate the mechanisms by which DC modulates GC cell proliferation, apoptosis, and migration.
Materials And Methods
. MKN-45 cells were used for in vitro studies, and xenograft tumor models were established using BALB/c nude mice for in vivo evaluation. Bioinformatics analysis predicted core targets. CCK-8, flow cytometry, wound healing, Transwell, and fluorescence microscopy assays were performed to assess proliferation, cell-cycle distribution, apoptosis, migration, and ROS levels. Expression of proteins in the EGFR/MAPK, EGFR/AKT, and AKT/GSK-3β/β-catenin pathways was determined by Western blotting.
Results
. In vitro, DC significantly inhibited GC cell proliferation and induced morphological changes. DC induced cell cycle arrest in the G0/G1 phase and promoted mitochondria-dependent apoptosis by modulating EGFR/MAPK signaling, while inhibiting migration through the AKT/GSK-3β/β-catenin pathway. Mechanistically, DC inhibited EGFR activation and elevated ROS levels. The EGFR agonist NSC228155 reversed these effects, confirming dependence on EGFR-ROS signaling. In vivo, DC dose‑dependently inhibited tumor growth, with medium/high doses outperforming 5‑fluorouracil. Histological examination of major organs showed no significant abnormalities, confirming low toxicity at therapeutic doses.
Conclusions
. DC inhibited proliferation, induced cell cycle arrest and apoptosis, and suppressed migration in GC cells by modulating EGFR-related ROS-dependent signaling pathways.