Neuroblastoma is a rare childhood cancer with poor outcome.
Though investigations in identification of biologic and genetic markers, neuroblastoma is still a therapeutic challenge, especially because of chemoresistance. Notably, chemoresistance is mainly based on the upregulation of ABC transporters. Our previous studies have shown that HMG-CoA reductase inhibitors statins are able to downregulate and alter the glycosylation of the most prominent ABC transporter ABCB1 (Sieczkowski et al, 2010; Werner et al, 2013). In this study, we wanted to investigate the underlying mechanism for the downregulation as well as altered glycosylation of ABCB1 in more detail. Data presented here were performed with neuroblastoma cell line SH-SY5Y in vitro as well in vivo using xenograft murine model. In both studies we found that simvastatin induces apoptosis in these cells which could be prevented by addition of dolichol. Moreover, simvastatin inhibits efflux activity of ABCB1 and depletes cells from endogenous dolichol which can partly explain the downregulation and altered glycosylation of ABCB1.
In conclusion, these data provide novel evidence to use statins in anticancer strategies.