Matrine enhances cisplatin sensitivity in oral squamous cell carcinoma through regulation of oxidative stress and apoptosis

Cisplatin resistance remains a major limitation in the treatment of oral squamous cell carcinoma (OSCC), often associated with altered oxidative stress. This study aimed to evaluate whether matrine can enhance cisplatin sensitivity in OSCC cells and explore its potential underlying mechanisms.Bioinformatics analysis and molecular docking were used to predict potential targets and pathways. In vitro experiments were conducted using CAL27 and cisplatin-resistant CAL27/DDP cells. Cell viability was assessed by CCK-8 assay, and drug interaction was evaluated using combination index (CI). Colony formation, reactive oxygen species (ROS), glutathione (GSH), apoptosis, and protein expression were analyzed.A total of 104 matrine-related targets and 21 overlapping genes were identified. Enrichment analysis suggested that oxidative stress-related pathways may be involved. Matrine alone showed limited cytotoxicity, while it significantly enhanced cisplatin sensitivity, reducing IC50 from 8.340 μM to 2.703 μM (P < 0.01) with CI values <1. Combined treatment decreased GSH and increased ROS (P < 0.001), accompanied by increased apoptosis (P < 0.001). The expression of Nrf2-related antioxidant proteins was reduced, while apoptotic protein levels were increased.Matrine enhances cisplatin sensitivity in OSCC cells, which may be associated with the regulation of oxidative stress and apoptosis. These findings suggest that matrine may serve as a potential chemosensitizing agent.