Rewiring of Lipid Metabolism and Storage in Ovarian Cancer Cells after Anti-VEGF Therapy

Cells. 2019 Dec 9;8(12):1601. doi: 10.3390/cells8121601.


Anti-angiogenic therapy triggers metabolic alterations in experimental and human tumors, the best characterized being exacerbated glycolysis and lactate production. By using both Liquid Chromatography-Mass Spectrometry (LC-MS) and Nuclear Magnetic Resonance (NMR) analysis, we found that treatment of ovarian cancer xenografts with the anti-Vascular Endothelial Growth Factor (VEGF) neutralizing antibody bevacizumab caused marked alterations of the tumor lipidomic profile, including increased levels of triacylglycerols and reduced saturation of lipid chains. Moreover, transcriptome analysis uncovered up-regulation of pathways involved in lipid metabolism. These alterations were accompanied by increased accumulation of lipid droplets in tumors. This phenomenon was reproduced under hypoxic conditions in vitro, where it mainly depended from uptake of exogenous lipids and was counteracted by treatment with the Liver X Receptor (LXR)-agonist GW3965, which inhibited cancer cell viability selectively under reduced serum conditions. This multi-level analysis indicates alterations of lipid metabolism following anti-VEGF therapy in ovarian cancer xenografts and suggests that LXR-agonists might empower anti-tumor effects of bevacizumab.

Keywords: LXR agonist; bevacizumab; lipid droplets; metabolism; ovarian cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Benzoates / therapeutic use
  • Benzylamines / therapeutic use
  • Bevacizumab / therapeutic use
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Female
  • Humans
  • Immunohistochemistry
  • Lipid Metabolism / drug effects*
  • Magnetic Resonance Spectroscopy
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / metabolism*
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Vascular Endothelial Growth Factor A / metabolism*
  • Xenograft Model Antitumor Assays


  • Benzoates
  • Benzylamines
  • GW 3965
  • Vascular Endothelial Growth Factor A
  • Bevacizumab