|
|
The tyrosine kinase inhibitor ZD6474 inhibits tumour growth
in an intracerebral rat glioma model
Sandstrom M, Johansson M, Andersson U, Bergh A, Bergenheim AT, Henriksson R
Department of Radiation Sciences, Oncology, Umea University, S-901 85 Umea,
Sweden.
Malignant glioma is characterised by extensive neovascularisation, principally
influenced by vascular endothelial growth factor (VEGF).
ZD6474 is a potent
inhibitor of VEGF-R2 tyrosine kinase activity, but with additional inhibitory
effects on other growth factors.
In this study, we have investigated the effects
of ZD6474 with regard to tumour growth, neovascularisation, proliferation and
apoptosis in the intracerebral rat glioma model, BT4C.
ZD6474 (50 and 100 mg
kg(-1)) was given as a daily oral gavage.
Animals were killed on day 19 and
tumour volume was measured.
Sections were stained for factor VIII, Ki-67 and for
apoptosis.
The ability of ZD6474 to inhibit cell growth directly was examined in
vitro, using the glioma cell line BT4C and the transformed rat brain endothelial
cell line RBE4.
Cell growth was analysed with fluorometric microculture
cytotoxicity assay to quantify the cytotoxic effects.
ZD6474 significantly
decreased tumour volume compared to controls.
Microvascular density increased
after treatment with ZD6474, and tumour cell proliferation index was reduced.
There was also an increase in tumour cell apoptosis.
In vitro, the growth of
both cell lines was significantly reduced.
The results reported justify further
experimental investigations concerning the effects of ZD6474 in malignant glioma
alone or in combination with other modalities.
PMID: 15305185 [PubMed - as supplied by publisher]
Source: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15305185&dopt=Abstract
|
