Abstract
Objective
Ovarian cancer is a common gynecological malignant tumor, and its incidence ranks high among female malignant tumors. Based on network pharmacology and bioinformatics analysis, the mechanism of GFC in the treatment of ovarian cancer was explored by in vitro and in vivo experiments.
Methods: Firstly, the common target genes of ovarian cancer and the effective chemical components of GFC were screened, and network pharmacology was used to identify the potential targets of GFC in the treatment of ovarian cancer. Then, the prediction results of network pharmacology were verified by cell and animal experiments. Finally, the use of LC-MS/MS of GFC representative compounds and the main effective component is analyzed.
Results: Effective chemical components of GFC can target 265 potential sites in ovarian cancer. Gene enrichment analysis has revealed that the dysregulation of glycolysis metabolism and its associated pathways are promising targets for treating ovarian cancer. Experimental results have demonstrated that cisplatin resistance in ovarian cancer is correlated with elevated glycolysis levels. When combined with cisplatin, GFC consistently suppresses glycolysis levels and the activity of its regulatory enzymes in A2780/DDP cells, while initially increasing and subsequently decreasing oxidative phosphorylation levels. Oxidative phosphorylation of ATP activating ROS caused mitochondrial autophagy and apoptosis. Animal studies have further confirmed that the combination treatment of GFC and cisplatin effectively inhibits tumor growth, as well as glycolysis and oxidative phosphorylation in mice.
Conclusions: GFC combined with cisplatin can rebalance energy metabolism and promote the apoptosis of ovarian cancer cells.