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

Resistance to chemotherapy represents a major obstacle to the successful treatment of gastric cancer (GC). This study aimed to investigate the role and underlying mechanism of baicalein in cisplatin resistance in gastric cancer through the OMA1/OPA1 axis.Baicalein treatment significantly increased mitochondrial fission and ROS levels in AGS cells, leading to reduced ATP production and consequently enhancing cisplatin-induced cytotoxicity in gastric cancer cells.Intriguingly,OMA1 expression was most significantly increased upon combined treatment with baicalein and cisplatin in AGS cells.In contrast,OPA1 expression was significantly reduced.Mechanistically, we define a signaling axis linking OMA1 to OPA1 and mitochondrial fission in Gastric cancer. Moreover, overexpression of OMA1 in AGS/DDP cells also significantly increased mitochondrial fission and ROS levels, decreased OPA1 protein expression and mitochondrial membrane potential, and reduced ATP production.Consistently, the cell viability and cell apoptosis assay showed that OMA1 overexpression synergistically enhancing cisplatin sensitivity in AGS/DDP cells.Taken together, all data in this study indicate that baicalein improves cisplatin resistance in gastric cancer through OMA1/OPA1 axis mediated mitochondrial dynamics,and repurpose baicalein as a potential agent to inhibit cisplatin resistance in GC.Furthermore,improve our knowledge about how OMA1 regulates mitochondria and provide justification for combining OMA1 overexpression with chemotherapy in GC.