The effects of antiepileptic drugs on the growth of glioblastoma cell lines.
The effects of antiepileptic drugs on the growth of glioblastoma cell lines.
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DOI：
10.1007/s11060-016-2056-6
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发表时间：
2016-05
影响因子：
3.9
通讯作者：
Lee ST
中科院分区：
文献类型：
--
作者：
Lee CY;Lai HY;Chiu A;Chan SH;Hsiao LP;Lee ST
为了确定抗癫痫药物化合物对胶质母细胞瘤细胞生长的影响，我们对胶质母细胞瘤细胞系进行筛选。用四甲基偶氮唑盐比色法检测不同抗癫痫药物对胶质母细胞瘤细胞的影响。对有明显抑制作用的化合物进行细胞周期分析。采用SPSS统计软件进行统计分析。筛选出的抗癫痫化合物包括卡马西平、乙硫胺、加巴喷丁、拉莫三嗪、左乙拉西坦、硫酸镁、奥卡西平、苯妥英钠、扑米酮、替加宾、托吡酯、丙戊酸和维巴匹林。地塞米松为阴性对照，替莫唑胺为阳性对照。我们的结果显示替莫唑胺和奥卡西平显著抑制胶质母细胞瘤细胞的生长，并在治疗浓度下达到IC50。筛选的其他抗癫痫药物在治疗浓度下无法达到IC50。奥卡西平的代谢产物也不能达到IC50。地塞米松、乙硫胺、左乙拉西坦和维甲菊酯对生长有一定的促进作用，但未达到统计学意义。研究中发现的乙硫胺、左乙拉西坦和维拉西坦的生长促进作用可能表明，这些化合物不应用于胶质母细胞瘤癫痫的预防或短期治疗。虽然丙戊酸和奥卡西平有效，但丙戊酸的所需剂量远远高于癫痫的治疗剂量，奥卡西平的代谢产物未能达到显著的生长抑制，排除了口服奥卡西平或丙戊酸作为胶质母细胞瘤单一治疗的可能性。将这些化合物用作局部治疗的可能性是未来的研究领域。
To determine the effects of antiepileptic drug compounds on glioblastoma cellular growth, we exposed glioblastoma cell lines to select antiepileptic drugs. The effects of selected antiepileptic drugs on glioblastoma cells were measured by MTT assay. For compounds showing significant inhibition, cell cycle analysis was performed. Statistical analysis was performed using SPSS. The antiepileptic compounds selected for screening included carbamazepine, ethosuximide, gabapentin, lamotrigine, levetiracetam, magnesium sulfate, oxcarbazepine, phenytoin, primidone, tiagabine, topiramate, valproic acid, and vigabatrin. Dexamethasone and temozolomide were used as a negative and positive control respectively. Our results showed temozolomide and oxcarbazepine significantly inhibited glioblastoma cell growth and reached IC50 at therapeutic concentrations. The other antiepileptic drugs screened were unable to reach IC50 at therapeutic concentrations. The metabolites of oxcarbazepine were also unable to reach IC50. Dexamethasone, ethosuximide, levetiracetam, and vigabatrin showed some growth enhancement though they did not reach statistical significance. The growth enhancement effects of ethosuximide, levetiracetam, and vigabatrin found in the study may indicate that these compounds should not be used for prophylaxis or short term treatment of epilepsy in glioblastoma. While valproic acid and oxcarbazepine were effective, the required dose of valproic acid was far above that used for the treatment of epilepsy and the metabolites of oxcarbazepine failed to reach significant growth inhibition ruling out the use of oral oxcarbazepine or valproic acid as monotherapy in glioblastoma. The possibility of using these compounds as local treatment is a future area of study.