Recombinant human VEGF165b protein is an effective anti-cancer agent in mice

被引：84

作者：

Rennel, Emma S. ^{[1
]}

Hamdollah-Zadeh, Maryam A. ^{[1
]}

Wheatley, Edward R. ^{[2
]}

Magnussen, Anette ^{[1
]}

Schueler, Yvonne ^{[1
]}

Kelly, Sara P. ^{[3
]}

Finucane, Ciara ^{[4
]}

Ellison, David ^{[4
]}

Cebe-Suarez, Stephanie ^{[5
]}

Ballmer-Hofer, Kurt ^{[5
]}

Mather, Stephen ^{[4
]}

Stewart, Lorna ^{[2
]}

Bates, David O. ^{[1
]}

Harper, Steven J. ^{[1
]}

机构：

[1] Univ Bristol, Sch Vet Sci, Dept Physiol & Pharmacol, Microvasc Res Labs, Bristol BS2 8EJ, Avon, England

[2] Canc Res Technol, London, England

[3] Univ Walk, Sch Med, Dept Physiol & Pharmacol, Bristol BS8 1TD, Avon, England

[4] Barts & London Queen Marys Sch Med & Dent, Nucl Med Res Lab, London, England

[5] Paul Scherrer Inst, Lab Biomol Res, CH-5232 Villigen, Switzerland

来源：

EUROPEAN JOURNAL OF CANCER | 2008年 / 44卷 / 13期

关键词：

VEGF; VEGF(165)b; anti-angiogenesis; cancer inhibition; pharmacokinetics; liver toxicity;

D O I：

10.1016/j.ejca.2008.05.027

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Tumour growth is dependent on angiogenesis, the key mediator of which is vascular endothelial growth factor-A (VEGF-A). VEGF-A exists as two families of alternatively spliced isoforms - pro-angiogenic VEGF(xxx) generated by proximal, and anti-angiogenic VEGF(xxx)b by distal splicing of exon 8. VEGF(165)b inhibits angiogenesis and is downregulated in tumours. Here, we show for the first time that administration of recombinant human VEGF(165)b inhibits colon carcinoma tumour growth and tumour vessel density in nude mice, with a terminal plasma half-life of 6.2 h and directly inhibited angiogenic parameters (endothelial sprouting, orientation and structure formation) in vitro. Intravenous injection of I-125-VEGF(165)b demonstrated significant tumour uptake lasting at least 24 h. No adverse effects on liver function or haemodynamics were observed. These results indicate that injected VEGF(165)b was taken up into the tumour as an effective anti-angiogenic cancer therapy, and provide proof of principle for the development of this anti-angiogenic growth factor splice isoform as a novel cancer therapy. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：1883 / 1894

页数：12

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