P08.41 The metabolic effect of bevacizumab in mutant IDH1 glioma cells assessed by NMR spectroscopy

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Introduction: Malignant gliomas are rapidly growing and invasive tumours that secrete vascular endothelial growth factor (VEGF) to stimulate tumour angiogenesis. Bevacizumab by neutralizing the biological activity of VEGF normalizes tumour vasculature, and inhibits further angiogenesis, thereby inhibiting tumour growth. However, the direct effects of bevacizumab on tumour cells metabolism remain poorly known. Our study was performed to assess the effects of bevacizumab on the metabolism of glioma cells carrying the IDH1 mutation [a mutation associated with better prognosis and treatment outcome]. Material and Methods: The effect of different time exposures (from 24h to 72h) and bevacizumab concentrations (0.1 mg/mL to 1 mg/mL) was assessed with the MTT Assay. VEGF secretion was assessed by immunoassay. 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: We have identified changes in glutamine group metabolites and lipids as metabolic markers of bevacizumab treatment on mIDH1-U87. Our data support the possibility of a functional tricarboxylic acid cycle in these cells that uses glutamine as an alternative nutrient input (anaplerosis).

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