Effect of VEGF receptor inhibitor PTK787/ZK222548 combined with ionizing radiation on endothelial cells and tumour growth.
In: British Journal of Cancer, Jg. 85 (2001-12-15), Heft 12, S. 2010-2016
Online
academicJournal
Zugriff:
The vascular endothelial growth factor (VEGF) receptor is a major target for anti-angiogenesis-based cancer treatment. Here we report the treatment effect of ionizing radiation in combination with the novel orally bioavailable VEGF receptor tyrosine kinase inhibitor PTK787/ZK222584 on endothelial cell proliferation in vitro and with tumour xenografts in vivo. Combined treatment of human umbilical vein endothelial cells with increasing doses of PTK787/ZK222584 and ionizing radiation abrogated VEGF-dependent proliferation in a dose-dependent way, but inhibition of endothelial cell proliferation was not due to apoptosis induction. In vivo, a combined treatment regimen of PTK787/ZK222584 (4 x 100 mg/kg) during 4 consecutive days in combination with ionizing radiation (4 x 3 Gy) exerted a substantial tumour growth delay for radiation-resistant p53-disfunctional tumour xenografts derived from SW480 colon adenocarcinoma cells while each treatment modality alone had only a minimal effect on tumour size and neovascularization. SW480 tumours from animals that received a combined treatment regimen, displayed not only an extended tumour growth delay but also a significant decrease in the number of microvessels in the tumour xenograft. These results support the model of a cooperative antitumoural effect of angiogenesis inhibitor and irradiation and show that the orally bioavailable VEGF receptor tyrosine kinase inhibitor PTK787/ZK222584 is suitable for combination therapy with irradiation. [ABSTRACT FROM AUTHOR]
Titel: |
Effect of VEGF receptor inhibitor PTK787/ZK222548 combined with ionizing radiation on endothelial cells and tumour growth.
|
---|---|
Autor/in / Beteiligte Person: | Hess, C ; Vuong, V ; Hegyi, I ; Riesterer, O ; Wood, J ; Fabbro, D ; Glanzmann, C ; Bodis, S ; Pruschy, M |
Link: | |
Zeitschrift: | British Journal of Cancer, Jg. 85 (2001-12-15), Heft 12, S. 2010-2016 |
Veröffentlichung: | 2001 |
Medientyp: | academicJournal |
ISSN: | 0007-0920 (print) |
DOI: | 10.1054/bjoc.2001.2166 |
Schlagwort: |
|
Sonstiges: |
|