Correlation of Hypoxia-Inducible Factor 1{alpha} with Angiogenesis in Liver Tumors After Transcatheter Arterial Embolization in an Animal Model

Journal Article · Sun Aug 15 00:00:00 EDT 2010 · Cardiovascular and Interventional Radiology

DOI:https://doi.org/10.1007/S00270-009-9762-9· OSTI ID:21428957

Bin, Liang; Feng, Gan-Sheng ^[1]; Hanping, Wu ^[2]; Yong, Wang; Hui, Zhao; Jun, Qian; Huimin, Liang ^[1]

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1. Huazhong University of Science and Technology, Department of Radiology, Union Hospital, Tongji Medical College (China)
2. Case Western Reserve University, Department of Radiology, University Hospitals Case Medical Center (United States)

This study sought to determine the expression of hypoxia-inducible factor 1{alpha} (HIF-1{alpha}) and its relation to angiogenesis in liver tumors after transcatheter arterial embolization (TAE) in an animal model. A total of 20 New Zealand White rabbits were implanted with VX2 tumor in liver. TAE-treated group animals (n = 10) received TAE with polyvinyl alcohol particles. Control group animals (n = 10) received sham embolization with distilled water. Six hours or 3 days after TAE, animals were humanely killed, and tumor samples were collected. Immunohistochemical staining was performed to evaluate HIF-1{alpha} and vascular endothelial growth factor (VEGF) protein expression and microvessel density (MVD). Real-time polymerase chain reaction was performed to examine VEGF mRNA levels. The levels of HIF-1{alpha} protein were significantly higher in TAE-treated tumors than those in the control tumors (P = 0.001). HIF-1{alpha} protein was expressed in viable tumor cells that were located predominantly at the periphery of necrotic tumor regions. The levels of VEGF protein and mRNA, and mean MVD were significantly increased in TAE-treated tumors compared with the control tumors (P = 0.001, 0.000, and 0.001, respectively). HIF-1{alpha} protein level was significantly correlated with VEGF mRNA (r = 0.612, P = 0.004) and protein (r = 0.554, P = 0.011), and MVD (r = 0.683, P = 0.001). We conclude that HIF-1{alpha} is overexpressed in VX2 tumors treated with TAE as a result of intratumoral hypoxia generated by the procedure and involved in activation of the TAE-associated tumor angiogenesis. HIF-1{alpha} might represent a promising therapeutic target for antiangiogenesis in combination with TAE against liver tumors.

• OSTI ID: 21428957
• Journal Information: Cardiovascular and Interventional Radiology, Vol. 33, Issue 4; Other Information: DOI: 10.1007/s00270-009-9762-9; Copyright (c) 2010 Springer Science+Business Media, LLC and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE); ISSN 0174-1551
• Country of Publication: United States
• Language: English

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