The Vascular Endothelial Growth Factor Receptor-2 Tyrosine Kinase Inhibitor Cediranib (Recentin; AZD2171) Inhibits Endothelial Cell Function and Growth of Human Renal Tumor Xenografts
Received 30 June 2008; received in revised form 3 September 2008; accepted 20 October 2008.
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.
∗Department of Radiation Oncology, University of Florida, Gainesville, FL
†Cancer Bioscience, AstraZeneca, Alderley Park, Macclesfield, Cheshire, United Kingdom
Reprint requests to: Dietmar W. Siemann, Ph.D., Department of Radiation Oncology, University of Florida, 2000 S.W. Archer Road, Gainesville, FL 32610. Tel: (352) 265-0287; Fax: (352) 265-0759
Supported in part by a grant from AstraZeneca and US Public Health Service Grant CA089655 from the U.S. National Cancer Institute.
Conflict of interest: These studies were supported in part by a research grant to Dr. Siemann from AstraZeneca. Dr. Juliane Jürgensmeier is an employee of AstraZeneca.
ABSTRACT