Ferroptosis in Endometrial Cancer cells Induced by Erastin-Loaded Hydrogels
Objective To induce ferroptosis in human endometrial cancer cells(Ishikawa)by a sustained-release thermo-sensitive hydrogel based on poloxamer 407(P407)containing Erastin.Methods The physical characterization,phase tran-sition time,and sustained release properties of Erastin-loaded hydrogel complex(P407Era)were constructed and evaluated.The experiment was divided into a control control(Ctrl)group,hydrogel(P407)group,erastin-treated(Erastin)group,and hydrogel-loaded Erastin(P407Era)group.CCK-8 assay,ROS kit,and TUNEL assay kit were used to detect cell pro-liferation,intracellular ROS,and cell apoptosis,respectively.Cell mitochondrial membrane potential and Fe2+in mitochon-dria were observed using Mito-Tracker Red CMXRos and Mito-FerroGreen,respectively.Immunofluorescence and RT-qPCR were employed to determine the expressions of ferroptosis-related molecules.Results The phase change time of P407 was negatively correlated with concentration,and the P407 with a concentration of 18%had better drug sustained release performance.Compared with the conditions in the Ctrl group,the Ishikawa cell proliferation,migration and invasion were significantly inhibited in the P407,Erastin,and P407Era groups,and the P407Era group had more inhibition than the Erastin group.Compared with the Ctrl group,the Erastin and P407Era groups had significantly increased ROS and relative amount of cell apoptosis,decreased mitochondrial membrane potential of cells,elevated Fe2+in mitochondria,and reduced GPX4,with no marked change in the NRF2.Additionally,the mRNA expressions of TFR1,NCOA4,and P53 in the Erastin group and the P407Era group were significantly increased.Conclusion Erastin-loaded P407 induces ferroptosis in human endome-trial cancer cells.
国家科技期刊平台
NSTL
万方数据
