Repurposing trifluoperazine as a potential therapeutic agent for ovarian cancer: mechanistic insight via SRC/PI3K/AKT signaling pathway inhibition

This study evaluates the efficacy of trifluoperazine in treating ovarian cancer and investigates its potential molecular mechanisms through in vitro and in vivo experiments, as well as network pharmacology analysis. We used the CCK-8 assay to assess cell proliferation in five ovarian cancer cell lines (ES-2, SK-OV-3, OVCAR-3, OV-90, ID8). We performed scratch and Transwell assays on SK-OV-3 and ID8 cells to evaluate their migration and invasion capabilities. Apoptosis, proliferation, and reactive oxygen species (ROS) levels in ID8 cells were measured using Acridine Orange/Propidium Iodide (AO/PI) staining, EdU assays, and ROS assays, respectively. A xenograft mouse model was employed to assess the effect of trifluoperazine on tumor growth. Network pharmacology was used to identify common targets between trifluoperazine and ovarian cancer, followed by Western blot (WB) experiments to validate the protein expression levels of the SRC/PI3K/Akt signaling pathway. Trifluoperazine inhibited cell growth in a dose-dependent manner, with ES-2 cells showing the greatest sensitivity. Migration, invasion, and proliferation of SK-OV-3 and ID8 cells were significantly reduced, while apoptosis and ROS levels were increased. In vivo, trifluoperazine inhibited tumor growth, with only a slight decrease in body weight observed. Network pharmacology identified 110 common targets, with the main targets enriched in the PI3K-Akt pathway. WB analysis confirmed the downregulation of SRC, PI3K, and Akt proteins in cells treated with trifluoperazine. Trifluoperazine inhibits ovarian cancer progression in vitro and in vivo by targeting the SRC/PI3K/Akt signaling pathway, providing a potential new therapeutic strategy for ovarian cancer.