Antiangiogenic effects of pazopanib in xenograft hepatocellular carcinoma models: evaluation by quantitative contrast-enhanced ultrasonography

BMC Cancer

Research Article

Hong Ding¹  Pei-Li Fan¹  Ju-Bo Zhang²  Wei Zhang²  Wei-Zhong Wu²  Peng-Yuan Zhuang²  Zhao-You Tang²  Hua-Xiang Xu²  Dong-Mei Gao²  Hui-Chuan Sun²  Ling-Qun Kong²  Yu-Quan Xiong²  Lu Wang²  Xiao-Dong Zhu² 

[1] Department of Ultrasound, Zhongshan Hospital, Fudan University, 200032, Shanghai, P.R. China;Liver Cancer Institute and Zhongshan Hospital, Fudan University, 200032, Shanghai, P.R. China;

关键词: Area Under Curve;    Pazopanib;    Mean Transit Time;    Antiangiogenic Therapy;    Increase Signal Intensity;   

DOI  :  10.1186/1471-2407-11-28

 received in 2010-05-19, accepted in 2011-01-20,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundAntiangiogenesis is a promising therapy for advanced hepatocellular carcinoma (HCC), but the effects are difficult to be evaluated. Pazopanib (GW786034B) is a pan-vascular endothelial growth factor receptor inhibitor, the antitumor effects or antiangiogenic effects haven't been investigated in HCC.MethodsIn vitro direct effects of pazopanib on human HCC cell lines and endothelial cells were evaluated. In vivo antitumor effects were evaluated in three xenograft nude mice models. In the subcutaneous HCCLM3 model, intratumoral blood perfusion was detected by contrast-enhanced ultrasonography (CEUS), and serial quantitative parameters were profiled from the time-intensity curves of ultrasonograms.ResultsIn vitro proliferation of various HCC cell lines were not inhibited by pazopanib. Pazopanib inhibited migration and invasion and induced apoptosis significantly in two HCC cell lines, HCCLM3 and PLC/PRF/5. Proliferation, migration, and tubule formation of human umbilical vein endothelial cells were inhibited by pazopanib in a dose-dependent manner. In vivo tumor growth was significantly inhibited by pazopanib in HCCLM3, HepG2, and PLC/PRF/5 xenograft models. Various intratumoral perfusion parameters changed over time, and the signal intensity was significantly impaired in the treated tumors before the treatment efficacy on tumor size could be observed. Mean transit time of the contrast media in hotspot areas of the tumors was reversely correlated with intratumoral microvessel density.ConclusionsAntitumor effects of pazopanib in HCC xenografts may owe to its antiangiogenic effects, and the in vivo antiangiogenic effects could be evaluated by quantitative CEUS.

【 授权许可】

Unknown   
© Zhu et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.