Schizandrin B inhibits the cis-DDP-induced apoptosis of HK-2 cells by activating ERK/NF-κB signaling to regulate the expression of surviving

The nephrotoxicity of cisplatin limits its clinical application. Schizandrin B (SchB) has been demonstrated to have a variety of potential cytoprotective activities. The present study explored the molecular mechanisms by which SchB inhibits the dichlorodiammine platinum (DDP)-induced apoptosis of HK-2 proximal tubule epithelial cells. In vitro assays demonstrated that SchB increased the viability of HK-2 cells, alleviated the cis-DDP-induced activation of caspase-3, reduced apoptosis and improved the nuclear morphology of HK-2 cells. Additionally, the mechanism underlying the cis-DDP-induced apoptosis was indicated to involve the activation of p53, c-Jun-N-terminal kinase (JNK) and p38 signaling. Furthermore, SchB was demonstrated to activate extracellular signal-regulated kinase (ERK) and nuclear factor κB (NF-κB) signaling, and induce the expression of survivin. The inhibition of ERK and NF-κB signaling using U0126 and pyrollidine dithiocarbamate, respectively, inhibited the expression of survivin, whereas blocking the expression of survivin using small interfering RNA inhibited the alleviating effect of SchB on cis-DDP-induced apoptosis as indicated by a reduction in cleaved caspase-3 expression. In conclusion, SchB regulates ERK/NF-κB signaling to induce the expression of survivin, thereby alleviating cis-DDP-induced renal injury.