Proliferation, migration and invasion of human glioma cells exposed to paclitaxel (Taxol) in vitro

Abstract

Summary Paclitaxel (Taxol), an anti-cancer drug derived from Taxus species, was tested for its anti-migrational, anti-invasive and antiproliferative effect on two human glioma cell lines (GaMg and D-54Mg) grown as multicellular tumour spheroids. In addition, the direct effect of paclitaxel on glioma cells was studied using flow cytometry and scanning confocal microscopy. Both cell lines showed a dose-dependent growth and migratory response to paclitaxel. The GaMg cells were found to be 5-10 times more sensitive to paclitaxel than D-54Mg cells. Paclitaxel also proved to be remarkably effective in preventing invasion in a co-culture system in which tumour spheroids were confronted with fetal rat brain cell aggregates. Control experiments with Cremophor EL (the solvent of paclitaxel for clinical use) in this study showed no effect on tumour cell migration, cell proliferation or cell invasion. Scanning confocal microscopy of both cell lines showed an extensive random organization of the microtubules in the cytoplasm. After paclitaxel exposure, the GaMg and the D-54Mg cells exhibited a fragmentation of the nuclear material, indicating a possible induction of apoptosis. In line with this, flow cytometric DNA histograms showed an accumulation of cells in the G/M phase of the cell cycle after 24 h of paclitaxel exposure. After 48 h, a deterioration of the DNA histograms was observed indicating nuclear fragmentation.

A new superinvasive in vitro phenotype induced by selection of human breast carcinoma cells with the chemotherapeutic drugs paclitaxel and doxorubicin

“…This was not observed with the parental cell line. Enhanced invasiveness following paclitaxel treatment was unexpected, in the context of previous published results (Stearns and Wang, 1992;Terzis et al, 1997;Westerlund et al, 1997;Liu et al, 1998;Sgadari et al, 2000). The data presented clearly demonstrate that the superinvasive cells display reduced attachment to ECM proteins coupled with increased motility.…”

Temozolomide induces apoptosis and senescence in glioma cells cultured as multicellular spheroids

“…To some extent, the three-dimensional spheroidal cell culture mimics the in vivo situation more closely than two-dimensional culture systems and is suitable for in vitro testing of cytotoxic substances (Terzis et al, 1997(Terzis et al, , 1998. Cells inside a spheroid are facing respiratory stress, lack of nutrients and lack of growth factors.…”

“…The spheroid model furthermore allows analysing the potential of the drug to influence one of the most dangerous properties of glioblastoma cells, the invasion of neighbouring brain tissue (Terzis et al, 1997(Terzis et al, , 1998. In a confrontation study, we could show that temozolomide is able to reduce the invasiveness of glioblastoma cells into foetal brain aggregates.…”

“…We have chosen two glioma cell lines to study the effects of temozolomide on glioma spheroid cultures. The U87MG cell line contains a functional p53 protein and was described to be sensitive to cytostatic drugs (Li et al, 1997), while the GaMG cell line was described to be relatively resistant to these compounds (Terzis et al, 1997).…”

Convection enhanced delivery for treating brain tumors and selected neurological disorders: symposium review

“…(Department of Neurosurgery, University of Munich, Germany) described a collaborative phase I/II study of taxol infusion by CED in nine patients with recurrent glioblastoma multiforme. He noted that earlier studies of taxol in vitro showed that it destroyed targeted cells but in vivo studies showed it to have little to no efficacy owing to its inability to cross the blood-brain barrier [17][18][19][20][21][22][23]. The trial he described involved the implantation of two ventricular catheters into the geometric center of the tumors as determined by MRI and later by fluorodeoxyglucosepositron emission tomography (FDG-PET).…”