Combining Dexamethasone and D-Methionine Provides Greater Protection Against Cisplatin- and Radiation-Induced Cytotoxicity in the Organ-of-Corti-Derived OC-k3 Cell Line: An In Vitro Study

Background/Objectives: Nasopharyngeal cancer generally has a good survival rate with chemoradiotherapy, but a significant side effect is irreversible hearing loss, for which there is currently no preventive intervention. Given that dexamethasone (Dex) and D-methionine (dMet) have individually shown potential to prevent hearing loss in in vitro and animal studies, we hypothesized that combining Dex and dMet may offer greater protection against cytotoxicity induced by cisplatin and radiation treatments. Methods: Organ-of-Corti-derived OC-k3 cells exposed to cisplatin and/or radiation were used as an in vitro model of treatment-induced cytotoxicity to investigate the protective mechanisms of Dex and dMet. Results: Dex was associated with reduced apoptosis, accompanied by decreased p53 phosphorylation and increased Bcl-XL expression. Dex also reduced COX2 expression and showed trends toward attenuation of ERK1/2 and NFκB signaling. Conversely, dMet effectively blocked cisplatin-induced apoptosis but did not protect against radiation-induced cytotoxicity. Conclusions: The combination of Dex and dMet provided greater protection against cisplatin- and radiation-induced cytotoxicity in the OC-k3 cells than either agent alone. These findings support further investigation of combined Dex and dMet as a potential strategy to mitigate treatment-induced ototoxicity.