The Zuo Jin Wan Formula Reverses Cisplatin Resistance in Gastric Cancer by Inhibiting the Mitochondrial Translocation of Dynamin-Related Protein 1 and Its Mediated Mitochondrial Fission and Mitophagy.
Gastric cancer is a major global health concern characterized by high incidence and mortality rates. One of the key challenges in treating gastric cancer is the development of resistance to chemotherapy drugs like cisplatin (DDP). This study aimed to investigate the efficacy of Zuo Jin Wan (ZJW), a traditional Chinese medicine, in overcoming DDP resistance in gastric cancer cells.
The research employed gastric cancer cells with DDP resistance, namely SGC7901/DDP and AGS/DDP, to explore the molecular mechanisms underlying ZJW's effects.
ZJW significantly reduced DDP resistance by inhibiting the phosphorylation and preventing mitochondrial translocation of Dynamin-related protein 1 (DRP1). ZJW treatment suppressed DRP1-mediated mitochondrial fission and mitophagy, thereby enhancing the sensitivity of resistant cells to DDP. Additionally, ZJW was observed to downregulate the AMPK signaling pathway, which plays a crucial role in DRP1 activation.
By modulating mitochondrial dynamics, ZJW disrupts protective mechanisms in resistant cancer cells, highlighting its potential as an adjunct therapy. This study underscores the therapeutic potential of integrating traditional Chinese medicine with conventional chemotherapy to combat drug resistance in gastric cancer.
The research employed gastric cancer cells with DDP resistance, namely SGC7901/DDP and AGS/DDP, to explore the molecular mechanisms underlying ZJW's effects.
ZJW significantly reduced DDP resistance by inhibiting the phosphorylation and preventing mitochondrial translocation of Dynamin-related protein 1 (DRP1). ZJW treatment suppressed DRP1-mediated mitochondrial fission and mitophagy, thereby enhancing the sensitivity of resistant cells to DDP. Additionally, ZJW was observed to downregulate the AMPK signaling pathway, which plays a crucial role in DRP1 activation.
By modulating mitochondrial dynamics, ZJW disrupts protective mechanisms in resistant cancer cells, highlighting its potential as an adjunct therapy. This study underscores the therapeutic potential of integrating traditional Chinese medicine with conventional chemotherapy to combat drug resistance in gastric cancer.