AS1517499 Protects Auditory Hair Cells Against Cisplatin‐Induced Damage In Vitro

ABSTRACT

Cisplatin‐induced ototoxicity is a common adverse effect of cisplatin‐based chemotherapy and significantly impairs the quality of life in cancer patients. Mechanistically, the STAT6 signaling pathway is critically involved in regulating the generation of pro‐inflammatory cytokines, which contributes to cisplatin‐induced ototoxicity. AS1517499, a novel STAT6 inhibitor, has been applied in several in vivo settings, including models of antigen‐induced airway hyper‐responsiveness, Graves' disease, and tumor progression. However, research into the effects of AS1517499 on the auditory system is limited. In this study, we preliminarily investigated the effects of AS1517499 on cisplatin‐induced ototoxicity. Our study showed that AS1517499 protects HEI‐OC1 cells from cisplatin‐induced injury. Specifically, this agent enhances cell survival, decreases apoptosis, and attenuates caspase‐3 activity. Taken together, these results suggest that AS1517499 exerts a protective effect on cisplatin‐related damage in this cellular model. Furthermore, AS1517499 has shown protective effects against damage in explant‐cultured cochlear hair cells (HCs). This study demonstrates that AS1517499 effectively mitigates cisplatin‐induced HC loss by inhibiting reactive oxygen species (ROS), thereby preventing HC apoptosis.