Treatment > STI571 · Temozolomide Investigations

Meeting Abstract

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.

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