Dioscin Inhibits Proliferation And Induces Apoptosis Of Gallbladder Cancer Cells And Its Mechanism

ObjectiveTo investigate the effects of dioscin on human gallbladder cancer(GBC)cells and the potential mechanisms underlying these effects.MethodsHuman NOZ and SGC996 cells were used to perform the experiments.CCK8 assay and colony formation assay were performed to evalue cell viability.Annexin V/PI staining assay for apoptosis were measured using flow cytometry.Hoechst 33342 staining,mitochondrial membrane potential(ΔΨm)assay and western blot analysis was used to evaluate the potential mechanisms of apoptosis.The effect of casticin or dioscin treatment in vivo was experimented with xenografted tumors.Reactive oxygen species(ROS)and glutathione(GSH)levels were measured to value the effects of ROS on apoptosis and cell viability,and the effect of dioscin treatment in vivo was experimented with xenografted tumors.ResultsThe results showed that dioscin and casticin significantly inhibited GBC cell proliferation.Moreover,dioscin induced gallbladder cancer cell apoptosis via mitochondrial dependent apoptotic signalling.Reactive oxygen species(ROS)and glutathione(GSH)levels were measured,and ROS scavengers completely inhibited dioscin-induced apoptosis,indicating that ROS play an essential role in GBC progression.Western blot analysis showed that AKT activity was significantly downregulated after dioscin treatment,and that inhibition/ectopic expression of AKT enhanced/abolished dioscin-induced apoptosis.Furthermore,we confirmed the relationship between ROS and the PI3K/AKT pathway and found that dioscin induced apoptosis by regμlating ROS-mediated PI3K/AKT signaling.ConclusionTaken together,these findings indicate that dioscin induces GBC apoptosis through inhibiting ROS-mediated PI3K/AKT signaling.