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

• Published in: Journal of vascular and interventional radiology Vol. 18; no. 5; pp. 639 - 645
• Main Authors: Rhee, Thomas K, Young, Joseph Y, Larson, Andrew C, Haines, 3rd, G Kenneth, Sato, Kent T, Salem, Riad, Mulcahy, Mary F, Kulik, Laura M, Paunesku, Tatjana, Woloschak, Gayle E, Omary, Reed A
• Format: Journal Article
• Language: English
• Published: United States 01.05.2007
• Subjects: 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
• ISSN: 1051-0443

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. 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). 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. 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.