Activation of β-catenin by inhibitors of glycogen synthase kinase-3 ameliorates cisplatin-induced cytotoxicity and pro-inflammatory cytokine expression in HEI-OC1 cells

摘要: Cisplatin is used in the treatment of a wide variety solid tumors, but its use limited by serious adverse effects, including ototoxicity. Glycogen synthase kinase-3 (GSK-3) ubiquitously expressed serine/threonine kinase that regulates cellular functions phosphorylating substrates. However, otoprotective effect GSK-3 inhibitors poorly understood. Here, we investigated whether involved cisplatin-induced ototoxicity HEI-OC1 cells and organs Corti (OCs). suppressed apoptosis determined decreased p53 activity, also expression PARP target genes such as p21 PUMA. The was mediated markedly increased nuclear β-catenin turn blocked translocation NF-κB. siRNA-mediated knockdown NF-κB genes, TNF-α IL-6. Our data suggest GSK-3/β-catenin pathway may play central role cisplatin-mediated cytotoxicity hair OCs vitro.