Type

Journal Article

Authors

Verena Amberger-Murphy
Martin Clynes
Paula Kinsella

Subjects

Biochemistry

Topics
glial fibrillary acidic protein inhibitory concentration 50 gene expression regulation enzymologic humans pharmacology metabolism protein tyrosine kinases docetaxel receptors platelet derived growth factor taxoids proto oncogene proteins c kit proto oncogene proteins c abl time factors drug effects piperazines pyrimidines glioma apoptosis cell line tumor cell proliferation imatinib antineoplastic combined chemotherapy protocols pathology antineoplastic agents

Imatinib and docetaxel in combination can effectively inhibit glioma invasion in an in vitro 3D invasion assay. (2010)

Abstract The main problem in the treatment of malignant astrocytomas is their invasive behaviour. Successful resection of the main tumour mass cannot prevent recurrence due to single cells invading the surrounding brain parenchyma at the time of diagnosis. The classical combination therapy, PCV (Procarbazine, CCNU and Vincristine) used for over 30 years; has shown its clinical effectiveness in the treatment of malignant astrocytomas and glioblastomas is still doubtful. Using an in vitro three dimensional invasion model, we tested the effect of the tyrosine kinase inhibitor imatinib and the microtubule inhibitor docetaxel on the invasion activity of a panel of astrocytic tumour cell lines, including two established glioma cell lines, IPSB-18 and SNB-19, and two primary cell lines, originating from glioblastomas, CLOM002 and UPHHJA, and in normal astrocytes. A dose response curve for each drug alone and in combination was determined. The half maximal inhibitory concentration (IC(50)) concentration of imatinib was between 15.7 and 18.7 μM, which did not affect invasion activity of the cell lines. The IC(50) concentration of docetaxel was between 0.7 and 19.8 nM, and at 14.9 nM docetaxel had a slight transient inhibitory effect on invasion activity of all tested cells. The combination of imatinib at 13.5 μM and docetaxel at 14.9 nM, however, synergistically inhibited cell growth and invasion activity and could not be reversed by drug removal. A combination treatment with tyrosine kinase inhibitors and cytotoxic drugs shows promise in tackling both glioma proliferation and invasion, and could present a new treatment regimen for malignant astrocytomas.
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Full list of authors on original publication

Verena Amberger-Murphy, Martin Clynes, Paula Kinsella

Experts in our system

1
Martin Clynes
Dublin City University
Total Publications: 209