Antiangiogenic effects of pazopanib in xenograft hepatocellular carcinoma models: evaluation by quantitative contrast-enhanced ultrasonography.
Antiangiogenic effects of pazopanib in xenograft hepatocellular carcinoma models: evaluation by quantitative contrast-enhanced ultrasonography.
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帕唑帕尼在异种移植肝细胞癌模型中的抗血管生成作用：通过定量超声造影评估
DOI：
10.1186/1471-2407-11-28
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发表时间：
2011-01-20
期刊：
影响因子：
3.8
通讯作者：
Sun HC
中科院分区：
文献类型：
--
作者：
Zhu XD;Zhang JB;Fan PL;Xiong YQ;Zhuang PY;Zhang W;Xu HX;Gao DM;Kong LQ;Wang L;Wu WZ;Tang ZY;Ding H;Sun HC
背景抗血管生成是治疗中晚期肝细胞癌的一种有前景的治疗方法，但其疗效难以评价。帕佐帕尼(Pazopanib，GW786034B)是一种泛血管内皮生长因子受体抑制剂，其抗肿瘤作用和抗血管生成作用在人肝癌中尚未见报道。对3种裸鼠移植瘤模型进行体内抗肿瘤实验。在HCCLM3皮下模型中，通过超声造影(CEUS)检测瘤内血流灌注，并根据超声时间-强度曲线绘制一系列定量参数。结果帕佐帕尼对多种肝癌细胞株的体外增殖无抑制作用。在HCCLM3和PLC/PRF/5两种肝癌细胞系中，帕佐帕尼均能显著抑制人脐静脉内皮细胞的迁移、侵袭和诱导细胞凋亡。在体内，帕佐帕尼显著抑制了HCCLM3、HepG2和PLC/PRF/5异种移植瘤模型的生长。肿瘤内的各种灌注参数随时间变化，在观察肿瘤大小的治疗效果之前，治疗后肿瘤的信号强度明显受损。对比剂在肿瘤热点区域的平均通过时间与瘤内微血管密度呈负相关。结论帕佐帕尼在肝癌移植瘤中的抗血管生成作用可能与其抗血管生成作用有关，体内抗血管生成作用可用定量超声评价。
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.
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影响因子：
11.2
作者：
Palmowski, Moritz;Huppert, Jochen;Kiessling, Fabian
通讯作者：
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