Effect of transcatheter arterial embolization on levels of hypoxia-inducible factor-1alpha in rabbit VX2 liver tumors

J Vasc Interv Radiol. 2007 May;18(5):639-45. doi: 10.1016/j.jvir.2007.02.031.

Abstract

Purpose: To test the hypothesis that transcatheter arterial embolization (TAE) of VX2 rabbit liver tumors increases the expression of hypoxia-inducible factor-1alpha (HIF-1alpha), a transcription factor that regulates the expression of pro-angiogenic genes.

Materials and methods: VX2 tumors were implanted in the livers of eight New Zealand white rabbits. Once tumor growth was seen at T2-weighted turbo spin-echo magnetic resonance (MR) imaging, four of the eight rabbits underwent TAE with 45-150-mum polyvinyl alcohol particles. The remaining four rabbits served as non-TAE controls. The TAE end point was stasis of antegrade blood flow. All rabbits were sacrificed for tumor harvest 2 hours after TAE. Tumor tissue and corresponding normal liver tissue in each rabbit liver were stained with anti-human HIF-1alpha monoclonal antibody and reviewed with light microscopy. Percentages of stained viable tumor and normal liver cells were compared by using the Mann-Whitney U test (alpha=0.05).

Results: In eight rabbits with 24 discrete liver tumors, the mean percentage (+/-standard deviation) of positive HIF-1alpha-stained cells in the TAE group was greater than that in the control group (19%+/-7.0 vs 12%+/-8.0, respectively) (P=.05). Normal liver tissue in both the TAE and control groups showed no HIF-1alpha staining.

Conclusion: Although HIF-1alpha is not expressed in normal rabbit liver parenchyma-even after TAE-HIF-1alpha expression is present in implanted VX2 rabbit liver tumors and significantly increased in lesions that have undergone embolization.

Publication types

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

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Chemoembolization, Therapeutic*
  • Disease Models, Animal
  • Feasibility Studies
  • Hypoxia-Inducible Factor 1, alpha Subunit / biosynthesis*
  • Liver Neoplasms, Experimental / genetics*
  • Liver Neoplasms, Experimental / therapy*
  • Rabbits

Substances

  • Hypoxia-Inducible Factor 1, alpha Subunit