The vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor cediranib (Recentin; AZD2171) inhibits endothelial cell function and growth of human renal tumor xenografts.
OBJECTIVE
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
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.
Siemann
Dietmar W
DW
Department of Radiation Oncology, University of Florida, Gainesville, FL 32610, USA. siemadw@ufl.edu
Brazelle
W D
WD
Jürgensmeier
Juliane M
JM
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D007680:Kidney Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011799:Quinazolines / Q000627:therapeutic use*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors*; D023041:Xenograft Model Antitumor Assays; D007211:Indoles
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D040301:Vascular Endothelial Growth Factor Receptor-2; C500926:cediranib; D007211:Indoles