ABSTRACT
PURPOSE: Ferroptosis is a new mode of regulated cell death, which is completely distinct from other cell death modes based on morphological, biochemical, and genetic criteria. This study evaluated the therapeutic role of ferroptosis in classic chemotherapy drugs, including the underlying mechanism. MATERIALS AND METHODS: Cell viabilitywas detected by using the methylthiazoltetrazlium dye uptake method. RNAiwas used to knockout iron-responsive element binding protein 2, and polymerase chain reaction, western blot was used to evaluate the efficiency. Intracellular reduced glutathione level and glutathione peroxidases activitywere determined by related assay kit. Intracellularreactive oxygen species levelswere determined by flowcytometry. Electron microscopywas used to observe ultrastructure changes in cell. RESULTS: Among five chemotherapeutic drugs screened in this study, cisplatin was found to be an inducer for both ferroptosis and apoptosis in A549 and HCT116 cells. The depletion of reduced glutathione caused by cisplatin and the inactivation of glutathione peroxidase played the vital role in the underlying mechanism. Besides, combination therapy of cisplatin and erastin showed significant synergistic effect on their anti-tumor activity. CONCLUSION: Ferroptosis had great potential to become a new approach in anti-tumor therapies and make up for some classic drugs, which open up a new way for their utility in clinic.
Subject(s)
Apoptosis , Blotting, Western , Carrier Proteins , Cell Death , Cisplatin , Drug Therapy , Glutathione , Glutathione Peroxidase , HCT116 Cells , Methods , Oxygen , Peroxidases , Polymerase Chain ReactionABSTRACT
OBJECTIVE@#To investigate the surgical treatment of cholesterol granuloma in middle ear.@*METHOD@#Nineteen patients of cholesterol granuloma in middle ear were retrospectively study. All the patients were treated with tympanic tube insertion, canal wall up mastoidectomy or intact-tympanic canal wall down mastoidectomy respectively.@*RESULT@#All the cases were followed up from 6 months to 3.3 years. Two patients recurred among the 4 patients treated with tympanic tube insertion, 3 patients recurred among 8 patients treated with canal wall up mastoidectomy, and no recurrence was found among 7 patients treated with intact-tympanic canal wall down mastoidectomy. 12 patients had their hearing improved obviously among 14 patients without recurrence.@*CONCLUSION@#For the juvenile patients with a short medical history occurred for the first time, tympanic tube insertion merely is a rea sonable choice after the factor of obstruction of the pharyngotympanic tube was removed. For the patients with a long medical history and comprehensive lesions, or occurred repeatedly after being treated with tympanic tube in sertion or canal wall up mastoidectomy, the intact-tympanic canal wall down mastoidectomy should be a good choice.