Correlation of hypoxia-inducible factor 1alpha with angiogenesis in liver tumors after transcatheter arterial embolization in an animal model.
This study sought to determine the expression of hypoxia-inducible factor 1alpha (HIF-1alpha) 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-1alpha 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-1alpha protein were significantly higher in TAE-treated tumors than those in the control tumors (P = 0.001). HIF-1alpha 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-1alpha 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-1alpha 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-1alpha might represent a promising therapeutic target for antiangiogenesis in combination with TAE against liver tumors.
Liang
Bin
B
Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jie-fang Road, Wuhan 430022, People's Republic of China.
Zheng
Chuan-Sheng
CS
Feng
Gan-Sheng
GS
Wu
Han-Ping
HP
Wang
Yong
Y
Zhao
Hui
H
Qian
Jun
J
Liang
Hui-Min
HM
D000818:Animals; D004195:Disease Models, Animal; D004621:Embolization, Therapeutic / Q000379:methods*; D000860:Hypoxia / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008099:Liver / Q000098:blood supply* / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000098:blood supply / Q000378:metabolism* / Q000628:therapy*; D055806:Microvessels; D009389:Neovascularization, Pathologic; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A