血管内皮生长因子受体-2酪氨酸激酶抑制剂西地尼布（Recentin；AZD2171）可抑制内皮细胞功能及人肾肿瘤异种移植瘤的生长。
The vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor cediranib (Recentin; AZD2171) inhibits endothelial cell function and growth of human renal tumor xenografts.
作者信息
Siemann Dietmar W, Brazelle W D, Jürgensmeier Juliane M
机构信息
Department of Radiation Oncology, University of Florida, Gainesville, FL 32610, USA.
出版信息
Int J Radiat Oncol Biol Phys. 2009 Mar 1;73(3):897-903. doi: 10.1016/j.ijrobp.2008.10.031.
Abstract
PURPOSE
The goal of this study was to examine the therapeutic potential of the vascular endothelial growth factor (VEGF) signaling inhibitor cediranib in a human model of renal cell carcinoma (Caki-1).
METHODS AND MATERIALS
The effects of cediranib treatment on in vitro endothelial cell function (proliferation, migration, and tube formation), as well as in vivo angiogenesis and tumor growth, were determined.
RESULTS
In vitro, cediranib significantly impaired the proliferation and migration of endothelial cells and their ability to form tubes, but had no effect on the proliferation of Caki-1 tumor cells. In vivo, cediranib significantly reduced Caki-1 tumor cell-induced angiogenesis, reduced tumor perfusion, and inhibited the growth of Caki-1 tumor xenografts.
CONCLUSIONS
The present results are consistent with the notion that inhibition of VEGF signaling leads to an indirect (i.e., antiangiogenic) antitumor effect, rather than a direct effect on tumor cells. These results further suggest that inhibition of VEGF signaling with cediranib may impair the growth of renal cell carcinoma.
摘要
目的
本研究的目的是在肾细胞癌（Caki-1）的人体模型中检验血管内皮生长因子（VEGF）信号抑制剂西地尼布的治疗潜力。
方法和材料
确定西地尼布治疗对体外内皮细胞功能（增殖、迁移和管形成）以及体内血管生成和肿瘤生长的影响。
结果
在体外，西地尼布显著损害内皮细胞的增殖和迁移及其形成管的能力，但对Caki-1肿瘤细胞的增殖没有影响。在体内，西地尼布显著减少Caki-1肿瘤细胞诱导的血管生成，降低肿瘤灌注，并抑制Caki-1肿瘤异种移植物的生长。
结论
目前的结果与以下观点一致，即抑制VEGF信号导致间接（即抗血管生成）抗肿瘤作用，而非对肿瘤细胞的直接作用。这些结果进一步表明，用西地尼布抑制VEGF信号可能损害肾细胞癌的生长。
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