Metabolic impact of anti-angiogenic agents on U87 glioma cells

Tanja Mesti1, Philippe Savarin2, Mohamed N Triba2

  • 1Laboratoire de Recherches Biochirurgicales, Université Paris Descartes, Hôpital Européen Georges Pompidou, Paris, France.

Plos One
|June 13, 2014
PubMed
Abstract

Insights

Bevacizumab (Bev) did not impact glioma cell metabolism, unlike VEGFR Tyrosine Kinase Inhibitor (TKI) SU1498, which increased lipids and decreased glycerophosphocholine. SU1498 affected proliferation and apoptosis, suggesting differential drug effects on glioma cells.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Glioma cells exhibit an autocrine loop involving vascular endothelial growth factor (VEGF) and its receptors (VEGFR).
  • The direct metabolic effects of VEGF pathway inhibitors, such as Bevacizumab (Bev) and VEGFR Tyrosine Kinase Inhibitors (TKIs), on glioma cells are not well understood.

Purpose of the Study:

  • To investigate the direct impact of Bevacizumab (Bev) and a selective VEGFR2 TKI, SU1498, on glioma cell metabolism and phenotype.
  • To compare the efficacy of Bev and SU1498 in targeting the VEGF autocrine loop in glioma cells.

Main Methods:

  • U87 glioma cells were treated with Bev or SU1498.
  • VEGF and VEGFR expression were analyzed using FACS and qRT-PCR.
  • VEGF secretion was measured via ELISA.
  • Cellular metabolism was assessed using High Resolution Magic Angle Spinning (HR-MAS) spectroscopy.

Main Results:

  • SU1498, but not Bev, significantly affected U87 cell proliferation and apoptosis.
  • Metabolomic analysis revealed SU1498 increased lipids and decreased glycerophosphocholine, with visible lipid droplet accumulation.
  • Bev showed no significant impact on cell metabolism.

Conclusions:

  • SU1498 demonstrates a clear impact on glioma cell proliferation, morphology, and metabolism, unlike Bevacizumab.
  • Bevacizumab is less likely to alter glioma cell phenotype through direct pressure on the VEGF autocrine loop.
  • Monitoring lipid changes with magnetic resonance spectroscopy (MRS) may serve as a marker for VEGFR TKI cytotoxicity in glioma patients.

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