Glycolytic inhibitor 2-deoxyglucose simultaneously targets cancer and endothelial cells to suppress neuroblastoma growth in mice
Journal
DMM Disease Models and Mechanisms
Journal Volume
8
Journal Issue
10
Pages
1247-1254
Date Issued
2015
Author(s)
Abstract
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 the 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 treated with 2DG by intraperitoneal injection twice a week for 3 weeks at 100 or 500 mg/kg body weight. We found that 2DG was effective in suppressing the growth of both MYCN-amplified SK-N-DZ and MYCN-non-amplified SK-N-AS neuroblastoma xenografts, which was associated with downregulation of HIF-1α, PDK1 and c-Myc, and a reduction in the number of tumor blood vessels. In vitro study showed that 2DG can suppress proliferation, cause apoptosis and reduce migration of murine endothelial cells, with inhibition of the formation of lamellipodia and filopodia and disorganization of F-actin filaments. The results suggest that 2DG might 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 patients with refractory neuroblastoma. ? 2015. Published by The Company of Biologists Ltd.
SDGs
Other Subjects
deoxyglucose; F actin; hypoxia inducible factor 1alpha; Myc protein; phosphoinositide dependent protein kinase 1; protein Bak; protein Bax; actin; deoxyglucose; hypoxia inducible factor 1alpha; Myc protein; protein Bak; protein Bax; protein serine threonine kinase; pyruvate dehydrogenase (acetyl-transferring) kinase; actin filament; animal cell; animal experiment; animal model; animal tissue; antiangiogenic activity; antiproliferative activity; apoptosis; Article; cancer cell; cancer inhibition; cell migration; controlled study; down regulation; drug targeting; endothelium cell; filopodium; human; human cell; immunohistochemistry; lamellipodium; male; mouse; mouse model; neuroblastoma; nonhuman; priority journal; tumor vascularization; tumor xenograft; animal; cell proliferation; drug effects; drug screening; endothelium cell; glycolysis; metabolism; neoplasm; neuroblastoma; nonobese diabetic mouse; pathology; pseudopodium; SCID mouse; tumor cell line; Actin Cytoskeleton; Actins; Animals; Apoptosis; bcl-2 Homologous Antagonist-Killer Protein; bcl-2-Associated X Protein; Cell Line, Tumor; Cell Proliferation; Deoxyglucose; Down-Regulation; Endothelial Cells; Glycolysis; Hypoxia-Inducible Factor 1, alpha Subunit; Immunohistochemistry; Mice, Inbred NOD; Mice, SCID; Neoplasms; Neuroblastoma; Protein-Serine-Threonine Kinases; Proto-Oncogene Proteins c-myc; Pseudopodia; Xenograft Model Antitumor Assays
Publisher
Company of Biologists Ltd
Type
journal article