Baicalein improves cisplatin resistance in gastric cancer through OMA1/OPA1 axis mediated mitochondrial dynamics

Chemoresistance represents a major obstacle to the successful treatment of gastric cancer (GC). This study aimed to investigate whether baicalein can help overcome cisplatin resistance in GC and explore the involvement of the OMA1/OPA1 axis in this effect. Treatment with baicalein significantly increased mitochondrial fission and ROS levels in AGS cells, reducing ATP production and sensitizing GC cells to cisplatin. Intriguingly, treating AGS cells with the combination of baicalein and cisplatin significantly increased OMA1 expression and reduced OPA1 expression. Mechanistically, we identified a signaling axis linking OMA1 to OPA1 and mitochondrial fission in GC. Moreover, OMA1 overexpression in AGS/DDP cells significantly increased mitochondrial fission and ROS levels, decreased the expression of the OPA1 protein and mitochondrial membrane potential (MMP), and reduced ATP production. Consistently, cell viability and cell apoptosis assays showed that OMA1 overexpression enhanced sensitivity to cisplatin in AGS/DDP cells. Taken together, this study indicated that baicalein improved cisplatin resistance in GC through OMA1/OPA1 axis-mediated modulation of mitochondrial dynamics. These findings support the repurposing of baicalein as a potential agent to reverse cisplatin resistance in GC. Furthermore, the results illuminate how OMA1 regulates mitochondrial dynamics and advocate for combining OMA1 overexpression with chemotherapy in GC.