Vandetanib inhibits cisplatin-resistant neuroblastoma tumor growth and invasion

Abstract

Resistance is the major cause of cisplatin treatment failure in neuroblastoma (NB). Vandetanib is widely used in the treatment of several cancers. In the present study, we aimed to determine the potential of vandetanib in cisplatin-resistant NB therapy. Immunohistochemistry (IHC) staining was employed to detect p-RET and CXCR4 expression in cisplatin-resistant or-sensitive NB tissues from patients. Vandetanib was added to treat selected cisplatin-resistant SH-SY5Y cells (SH-SY5Y-R); this was followed by CCK8 assay, colony formation assay, and invasion assay. Furthermore, the effect of vandetanib on subcutaneous tumor growth was investigated in mice. Our results demonstrated greater expression of p-RET and CXCR4 in cisplatin-resistant neuroblastomas (NBs). Vandetanib significantly inhibited SH-SY5Y-R cell proliferation, colony formation, and invasion, while downregulating p-RET and CXCR4 expression. Furthermore, vandetanib was as effective as high-dose cisplatin in impairing cisplatin-resistant NB subcutaneous tumor growth. Notably, vandetanib caused less severe liver toxicity in mice compared with high-dose cisplatin. In summary, this study identified Vandetanib as a potential drug for cisplatin-resistant NB treatment.