Nestler Ulf, Winking Michael, Böker Dieter-Karsten
Department of Neurosurgery, Justus Liebig University, Giessen, Germany.
Neurol Res. 2002 Jul;24(5):479-82. doi: 10.1179/016164102101200203.
In glioblastoma patients dexamethasone is routinely administered as an antiedematous drug. In contrast to its empirically proven effect, the biochemical way of action remains poorly understood. In order to assess whether a direct cytotoxic effect is present in vivo we compared dexamethasone levels in brain tumor specimens with its cytotoxic concentrations in cell culture. Biopsy specimens were taken during microsurgical tumor removal, homogenized and dexamethasone levels were measured by high pressure liquid chromatography. In cell culture we tested different concentrations of dexamethasone on A172, U87, U373 cells and on eleven primary glioblastoma cell lines. Furthermore a pilocytic astrocytoma I, an astrocytoma II and an oligodendroglioma III and a meningioma were examined. Cell viability was assessed using the Alamar Blue assay and the concentrations resulting in loss of 50% of the cell population were calculated (LD50). The average brain tumor tissue concentration of dexamethasone was 225 nanogram g(-1). The mean LD50 in cell culture ranged at 222 microgram ml(-1). We conclude that a direct cytotoxic effect of dexamethasone on brain tumor cells is not present in vivo because the tissue levels of the drug are about 1000 times lower than the LD50 in cell culture.
在胶质母细胞瘤患者中,地塞米松通常作为抗水肿药物使用。尽管其效果已得到经验证实,但其生化作用方式仍知之甚少。为了评估体内是否存在直接的细胞毒性作用,我们将脑肿瘤标本中的地塞米松水平与其在细胞培养中的细胞毒性浓度进行了比较。在显微手术切除肿瘤期间采集活检标本,将其匀浆,并通过高压液相色谱法测量地塞米松水平。在细胞培养中,我们在A172、U87、U373细胞以及11种原发性胶质母细胞瘤细胞系上测试了不同浓度的地塞米松。此外,还检测了1例毛细胞型星形细胞瘤、1例II级星形细胞瘤、1例III级少突胶质细胞瘤和1例脑膜瘤。使用alamar蓝分析法评估细胞活力,并计算导致50%细胞群体丧失的浓度(半数致死剂量,LD50)。地塞米松在脑肿瘤组织中的平均浓度为225纳克/克。细胞培养中的平均LD50范围为222微克/毫升。我们得出结论,地塞米松在体内对脑肿瘤细胞不存在直接的细胞毒性作用,因为药物的组织水平比细胞培养中的LD50低约1000倍。