In vitro nuclear magnetic resonance spectroscopy metabolic biomarkers for the combination of temozolomide with PI3K inhibition in paediatric glioblastoma cells

• DOI: 10.1371/journal.pone.0180263
• Publication Date: 2017-07-13T17:37:47Z
• Authors: Nada M. S. Al-Saffar; Alice Agliano; Lynley V. Marshall; L. Elizabeth Jackson; Geetha Balarajah; Jasmin Sidhu; Paul A. Clarke; Chris Jones; Paul Workman; Andrew D. J. Pearson; Martin O. Leach
• Keywords: Temozolomide; Phosphocholine; Dacarbazine; Choline

Recent experimental data showed that the PI3K pathway contributes to resistance temozolomide (TMZ) in paediatric glioblastoma and this effect is reversed by combination treatment of TMZ with a inhibitor. Our aim assess whether results metabolic changes are detectable nuclear magnetic resonance (NMR) spectroscopy, potentially providing biomarkers for inhibition treatment. Using two genetically distinct cell lines, SF188 KNS42, vitro 1H-NMR analysis following dual pan-Class I PI3K/mTOR inhibitor PI-103 resulted decrease lactate phosphocholine (PC) levels (P<0.02) relative control. In contrast, caused an increase glycerolphosphocholine (GPC) (P≤0.05). Combination effects both agents including PC while GPC (P<0.05). We also report protein expression HK2, LDHA CHKA likely mechanisms depletion PC, respectively. show our NMR-detected choline metabolites may have potential as non-invasive monitoring response inhibitors during clinical trials children glioblastoma, subject further vivo validation.