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Combination
of STI571 and temozolamide on inhibition of rat and human glioma cell lines
proliferation
F. S. Viola, F. Morrone, J. Stella, F. Spiller,
A. Battastini, C. H. Barrios
PUCRS
School of Medicine, Porto Alegre, RS, Brazil; UFRGS School of Pharmacy,
Department of Biochemistry, Porto Alegre, Brazil; PUCRS School of Medicine,
Porto Alegre, Brazil
Malignant gliomas are the most common primary brain
tumors in humans and despite available treatment they recur early.
STI571 (imatinib mesylate) is a kinase inhibitor which can lead to glioblastoma
growth arrest.
It has been established that among other kinases, STI571 inhibits the kinase
activity of the platelet-derived growth factor receptor (PDGFR).
Hyper-expression of this receptor and its ligand has been documented in some
malignant gliomas.
The cellular response of glioblastoma cells to STI571 does not appear to involve
an apoptotic mechanism, therefore, it could be useful to test the combination
with cytotoxic agents that promote programmed cell death.
Temozolomide is an alkylating agent that may induce apoptosis and has
characteristics that make it suitable for combination therapies, such as
broad-spectrum antitumor activity, the ability to cross the blood-brain barrier
and a good safety profile.
In this study we examine the effect on inhibition of PDGFR-mediated glioblastoma
proliferation by combination of an active kinase inhibitor (STI571) and
temozolomide.
Cell proliferation assay was performed by cell counting, and cytotoxicity of
STI571 (3MicroM, 6MicroM, 10MicroM), temozolamide (0.1MicroM, 1MicroM, 10MicroM)
and their combinations was assessed by using microculture MTT assay.
Results of cell counting demonstrated that STI571 and temozolamide alone
inhibited the growth of the C6 rat glioma cell line and the U138-MG human glioma
cell line in different concentrations; the combination of both agents
significantly inhibited cell proliferation in vitro but this inhibition was not
different from the one obtained with either agent alone.
Further experiments using MTT assay are being performed to confirm the
cytotoxicity results.
© Copyright 2003
American Society of Clinical Oncology All rights
reserved worldwide
Source:
http://www.asco.org/ac/1,1003,_12-002489-00_18-002003-00_19-00102715-00_29-00A,00.asp?cat=CNS+Tumors&parent=
Central+Nervous+System+Tumors&returnpid=2325&SubCat_ID=4
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