Glycolytic inhibitor 2 - deoxyglucose simultaneously targets cancer and endothelial cells to suppress neuroblastoma growth

Neuroblastoma is characterized by a wide range of clinical manifestations and associated with poor prognosis when there is amplification of MYCN oncogene or high expression of Myc oncoproteins. In a previous in vitro study, we found that glycolytic inhibitor 2-deoxyglucose (2DG) could suppress the growth of neuroblastoma cells, particularly in those with MYCN amplification. In this study, we established a mouse model of neuroblastoma xenografts with SK-N-DZ and SK-N-AS cells and treated with 100 mg/kg or 500 mg/kg of 2DG by intra-peritoneal injection twice a week for 3 consecutive weeks. We found that 2DG was effective to suppress the growth of both MYCN-amplified SK-N-DZ and MYCN-nonamplified SK-N-AS neuroblastoma xenografts, which was associated with down regulation of HIF-1α, PDK1 and c-Myc and reduction of tumor vessels. In vitro study showed that 2DG may suppress proliferation, cause apoptosis and reduce migration of murine endothelial cells with inhibition of lamellipodia and filopodia formation and disorganization of F-actin filaments. The results suggested that 2DG may simultaneously target cancer cells and endothelial cells in the neuroblastoma xenografts in mice regardless of the status of MYCN amplification, providing a potential therapeutic opportunity to use 2DG or other glycolytic inhibitors for the treatment of the patients with refractory neuroblastoma. D ise as e M od el s & M ec ha ni sm s D M M Ac ce pt ed m an us cr ip t