The mechanism of action of isorhamnetin on human ovarian cancer
Objective:To explore the mechanism of isorhamnetin in the treatment of ovarian cancer based on network pharmacology and cell experiments.Methods:The targets of isorhamnetin were collected by literature retrieval;to use Swiss Target Prediction to predict targets,to downloaded disease genes and find the intersection of drug and disease targets,and to perform protein-protein interaction(PPI)analysis.The core genes were obtained by Cytoscape,and enrichment analysis and molecular docking were performed.Human ovarian cancer SKOV3 cells were cultured in vitro,and treated with different concentrations of isorhamnetin(0,10,25)mg/L to compare the cell inhibition rate of each group,and the protein expressions of AKT,p-AKT,Bcl2 and BAX were compared.Results:96 potential targets and 14 core genes of isorhamnetin were found in ovarian cancer.The results of enrichment analysis suggested that the targets were related to serine/threonine protein kinase,mainly enriched in the PI3K/AKT pathway,and the molecular docking suggested that isorhamnetin had good binding activity with each target.The In vitro experiments confirmed that isorhamnetin could inhibit the activity of ovarian cancer cells.Flow cytometry detection found that the apoptosis rate of isorhamnetin treatment group increased.The results of Western blot showed that isorhamnetin could reduce the p-AKT/AKT protein expression ratio,reduce Bcl2 and increase BAX protein expression,thereby exerting anti-tumor effect.Conclusion:Isophoronin can promote the apoptosis of ovarian cancer cells.