In vitro assessment of Taxol for human glioblastoma: chemosensitivity and cellular locomotion.
Although the antineoplastic efficacy of Taxol against a variety of tumors has been established, it has only recently been used for malignant brain tumors. We evaluated in vitro chemosensitivity of glioblastoma to Taxol and the affect of Taxol on glioblastoma cell locomotion. The clonogenic assay was used to evaluate the chemosensitivity of five human glioblastomas and the C6 rat glioma. Cells exposed to Taxol (0-250 nM) were suspended in agar in capillary tubes. Following incubation, colonies were counted to determine percent survival. All six cell lines demonstrated sensitivity to Taxol (LD50 1 nM to > 250 nM). However, even at concentrations exceeding those achievable clinically, all cell lines had surviving cells, indicating a saturation threshold for Taxol cytotoxicity. Cell locomotion was evaluated using the radial dish assay to determine the rate of egress of cells from a region of high cell density to the periphery. Increasing Taxol concentration caused increased locomotion in all six cell lines (p < 0.0001). Although Taxol has significant cytocidal impact, it increases in vitro locomotion of glioblastoma cells. These findings suggest that the clinical use of Taxol for glioblastoma may slow the growth of bulk disease, but may also lead to increased tumor invasion.
Silbergeld
D L
DL
Department Neurological Surgery, Washington University School of Medicine, St Louis, MO 63110-1093, USA.
Chicoine
M R
MR
Madsen
C L
CL
D002465:Cell Movement / Q000187:drug effects; D005909:Glioblastoma / Q000188:drug therapy / Q000473:pathology*; D006801:Humans; D017239:Paclitaxel / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D017239:Paclitaxel