Network pharmacology and experimental methods to explore the mechanism of Poria extract in overcoming cisplatin-resistant ovarian cancer

Ovarian cancer is a common gynecological malignancy with a high incidence rate among female cancers. This study explored the mechanism of Poria extract in treating ovarian cancer through a combination of network pharmacology, bioinformatics analysis, and both in vitro and in vivo experimental validations. First, potential target genes associated with ovarian cancer and the active chemical components of Poria extract were identified using network pharmacology to determine possible therapeutic targets. Subsequently, these predictions were validated through cell culture and animal experiments. A total of 146 potential target sites were identified as being influenced by Poria extract's active components. Gene enrichment analysis indicated that dysregulated glycolysis metabolism and its related pathways are promising therapeutic targets for ovarian cancer. Experimental findings demonstrated that cisplatin resistance in ovarian cancer correlates with increased glycolytic activity. When administered in combination with cisplatin, Poria extract effectively suppresses glycolysis levels and the activity of its regulatory enzymes in A2780/DDP cells, while inducing an initial increase followed by a decrease in oxidative phosphorylation. The activation of ATP via oxidative phosphorylation leads to ROS accumulation, triggering mitochondrial autophagy and apoptosis. In vivo studies further confirmed that the combined treatment significantly inhibits tumor growth, as well as glycolysis and oxidative phosphorylation, in mice models. Overall, the combination of Poria extract and cisplatin can rebalance cellular energy metabolism and promote apoptosis in ovarian cancer cells.