TBIO-09. IN VITRO EVALUATION OF THE POTENTIAL OF GLUCOSE RESTRICTION AS AN ADJUVANT THERAPY FOR PAEDIATRIC BRAIN TUMOURS

Brain tumours are the most challenging cancers in relation to diagnosis, treatment and outcome. Under normal physiological conditions, brain cells metabolise glucose for energy. If glucose deprived they instead metabolise ketone bodies (KBs). Mitochondrial defects in brain tumours obviate this metabolic flexibility resulting in glucose dependence. Thus, a high fat, low carbohydrate ketogenic diet (KD) may control tumour growth. We evaluated glucose restriction on Ependymoma (BXD-1425, Epn1), pHGG (SF188, KNS42) and DIPG (HSJD07, HSJD013) cells using 17mM, 10mM (diabetic), 5mM (physiological), 3mM (hypoglycaemic), 1mM and 0mM glucose +/- KBs. Spheroid volume and metabolic activity were assessed and immunohistochemistry performed. There was no significant difference in metabolic activity as glucose concentration decreased. Spheroid size decreased in all cells as glucose concentration decreased and could not be rescued by KBs. All cells showed low expression of OXCT1 and BDH1 and were PKM2 positive with no significant variation with glucose concentration. Ki67 was maintained at all glucose concentrations. LC3B and p62 showed increased expression at lower glucose concentrations, unaffected by addition of KBs. Caspase-3 remained low regardless of glucose concentration except in DIPG cells where expression was consistently high. This implies that all cell lines evaluated were unable to adapt and initiated autophagy in response to reduced glucose concentrations. The significance of apoptotic cell death in DIPG cells is uncertain as it appears unrelated to glucose concentration. This shows that Ependymoma, pHGG and DIPG tumour cells are dependent on glucose for growth and provides evidence that these patients may respond to the KD.