Proliferation, migration and invasion of human glioma cells exposed to paclitaxel (Taxol) in vitro.
Proliferation, migration and invasion of human glioma cells exposed to paclitaxel (Taxol) in vitro.
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DOI：
10.1038/bjc.1997.298
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发表时间：
1997
影响因子：
8.8
通讯作者：
Gundersen G
中科院分区：
文献类型：
--
作者：
Terzis AJ;Thorsen F;Heese O;Visted T;Bjerkvig R;Dahl O;Arnold H;Gundersen G
紫杉醇 (Taxol) 是一种从红豆杉属植物中提取的抗癌药物，测试了其对两种生长为多细胞肿瘤球体的人神经胶质瘤细胞系（GaMg 和 D-54Mg）的抗迁移、抗侵袭和抗增殖作用。此外，使用流式细胞术和扫描共聚焦显微镜研究了紫杉醇对神经胶质瘤细胞的直接影响。两种细胞系均表现出对紫杉醇的剂量依赖性生长和迁移反应。研究发现 GaMg 细胞对紫杉醇的敏感性比 D-54Mg 细胞高 5-10 倍。事实证明，紫杉醇在预防共培养系统中的侵袭方面也非常有效，在共培养系统中，肿瘤球体与胎鼠脑细胞聚集体相对。本研究中Cremophor EL（临床用紫杉醇的溶剂）的对照实验显示对肿瘤细胞迁移、细胞增殖或细胞侵袭没有影响。两种细胞系的扫描共聚焦显微镜显示细胞质中微管的广泛随机组织。暴露于紫杉醇后，GaMg 和 D-54Mg 细胞表现出核材料碎裂，表明可能诱导细胞凋亡。与此相符，流式细胞术 DNA 直方图显示，在紫杉醇暴露 24 小时后，细胞周期的 G2/M 期细胞积累。 48 小时后，观察到 DNA 直方图恶化，表明核断裂。
Paclitaxel (Taxol), an anti-cancer drug derived from Taxus species, was tested for its anti-migrational, anti-invasive and anti-proliferative 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 G2/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.