Erythropoietin disrupts hypoxia-inducible factor signaling in ovarian cancer cells

Gynecol Oncol. 2006 Jan;100(1):14-9. doi: 10.1016/j.ygyno.2005.08.056. Epub 2005 Oct 13.

Abstract

Objective: The objective of this study was to evaluate the effects of recombinant erythropoietin (EPO) on HIF-1alpha induced angiogenic pathways in ovarian cancer cells.

Methods: Using Western blots and both quantitative and non-quantitative RT-PCR, HIF-1alpha protein and VEGF transcription levels were assessed. Cell growth was measured using flow cytometry.

Results: EPO treatment decreased hypoxia-induced HIF-1alpha protein levels and VEGF transcription, with no effect on cell growth. Inhibition of HIF-1alpha signaling by EPO was also observed in MCF-7 breast cancer cells.

Conclusion: These novel findings suggest that EPO may exhibit anti-angiogenic properties, thus encouraging further exploration of signaling pathways between EPO and HIF-1alpha.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Growth Processes / drug effects
  • Cell Hypoxia
  • Cell Line, Tumor
  • Erythropoietin / pharmacology*
  • Female
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / antagonists & inhibitors*
  • Hypoxia-Inducible Factor 1, alpha Subunit / biosynthesis
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism
  • Ovarian Neoplasms / blood supply*
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Receptors, Erythropoietin / biosynthesis
  • Receptors, Erythropoietin / genetics
  • Recombinant Proteins
  • Signal Transduction / drug effects
  • Transcription, Genetic / drug effects
  • Vascular Endothelial Growth Factor A / biosynthesis
  • Vascular Endothelial Growth Factor A / genetics

Substances

  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • RNA, Messenger
  • Receptors, Erythropoietin
  • Recombinant Proteins
  • Vascular Endothelial Growth Factor A
  • Erythropoietin