Role of autophagy in cisplatin-induced ototoxicity

Abstract

ObjectiveHearing loss is a major side effect of cisplatin chemotherapy. Although cell death in cisplatin-induced ototoxicity is primarily caused by apoptosis, the exact mechanism behind the ototoxic effects of cisplatin is not fully understood. Autophagy is generally known as a pro-survival mechanism that protects cells under starvation or stress conditions. However, recent research has reported that autophagy plays a functional role in cell death also. This study aimed to investigate the role of autophagy in cisplatin-induced ototoxicity in an auditory cell line. MethodsCultured HEI-OC1 cells were exposed to 30μM cisplatin for 48h, and cell viability was tested using MTT assays. To evaluate whether autophagy serves to cell death after cisplatin exposure, western blotting and immunofluorescence staining for LC3-II were performed. Markers of two autophagy-related pathways, mTOR and class III PI3K, were also investigated. ResultsThe formation of the autophagic protein LC3-II in response to 30μM cisplatin increased with time. The early upregulation of autophagy exerted cytoprotective activity via the class III PI3K pathway. But later increase in autophagy induced cell death by suppressing the mTOR pathway. ConclusionOur results prove that autophagy could induce cell death during cisplatin-induced ototoxicity, and modulating the autophagic pathway might be another strategy against cisplatin-induced ototoxicity.