Imatinib and Docetaxel in combination can effectively inhibit glioma invasion in an in vitro 3D invasion assay.
Kinsella, Paula (2011) Imatinib and Docetaxel in combination can effectively inhibit glioma invasion in an in vitro 3D invasion assay. Journal of Neuro-Oncology, 101 (2). pp. 189-198. ISSN 0167-594X
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The main problem in the treatment of malignant astrocytomas is their invasive behaviour. Even successful resection of the main tumour mass cannot prevent recurrence due to single cells, which have invaded the surrounding brain parenchyma already at the time of diagnosis. The classical combination therapy, PCV (Procarbazine, CCNU and Vincristine) has been used for over 30 years; however, its clinical effectiveness in the treatment of malignant astrocytomas and glioblastomas is still doubtful. Using an in vitro 3D 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. A dose response curve for each drug alone and in combination was determined. The half maximal inhibitory concentration (IC50) concentration of imatinib was between 15.7 µM and 18.7 µM, which did not affect invasion activity of the tested cell lines. The IC50 concentration of docetaxel was between 0.7 nM and 19.8 nM, and at 14.9 nM docetaxel had a slight transient inhibitory effect on invasion activity of all cell lines. 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 might be a promising step forward to tackle both glioma proliferation and invasion and could present a new treatment regimen for malignant astrocytomas.
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