NMR Metabolic Fingerprint of Bevacizumab in Mutant IDH1 Glioma Cells
INTRODUCTION: Our study was performed to assess the metabolic effects of bevacizumab on the glioma cells carrying the IDH1 mutation, a mutation associated with better prognosis and treatment outcome. Bevacizumab is known to inhibit tumour growth by neutralizing the biological activity of VEGF. However, the direct effects of bevacizumab on tumour cells metabolism remain poorly known.
MATERIAL AND METHODS: The immunoassay and MTT Assay were used to assess the concentration of secreted VEGF and cell viability after bevacizumab exposure. Metabolomic studies on cells were performed using High Resolution Magic Angle Spinning Spectroscopy (HR-MAS).
RESULTS: mIDH1-U87 cells secrete VEGF (13 ng/mL). Regardless bevacizumab had no cytotoxic effect, even after a 72 h exposure and with doses as high as 1 mg/mL. Yet, HRMAS analysis showed a significant effect of bevacizumab (0.1 mg/mL) on the metabolic phenotype of mIDH1-U87 cells with elevation of 2-hydroxyglutarate and changes in glutamine group metabolites (alanine, glutamate, glycine) and lipids (PUFA, glycerophosphocholine, and phosphocholine).
CONCLUSIONS: In mIDH1-U87 cells, changes in glutamine group metabolites and lipids were identified as metabolic markers of bevacizumab treatment. These data support the possibility of a functional tricarboxylic acid cycle in these cells that uses glutamine as an alternative nutrient input (anaplerosis).