地昔帕明对胶质瘤C6细胞增殖抑制的神经酰胺通路

目的:研究神经酰胺通路在抗抑郁药地昔帕明抑制大鼠胶质瘤C6细胞增殖及诱导细胞凋亡中的作用。方法:MTT法测定C6细胞活力;AnnexinⅤ/PI双染色流式细胞术对细胞早期凋亡进行定量分析。结果:地昔帕明(5~20μmol·L-1)浓度依赖性抑制C6细胞的增殖且与C2-神经酰胺具协同作用;10μmol·L-1神经酰胺合成酶抑制剂烟曲霉毒素(FB1)预处理18h可显著对抗地昔帕明对C6细胞增殖的抑制作用。地昔帕明(20μmol·L-1)可诱导C6细胞发生早期凋亡(13.1%),而FB1(10μmol·L-1)预处理对凋亡发生率无明显影响。结论:地昔帕明可通过增加神经酰胺从头合成抑制胶质瘤细胞C6的增殖。

Desipramine inhibited proliferation of glioma C6 cell via ceramide pathway

AIM:To investigate the role of ceramide in cell proliferation and early apoptos is induction in C6 glioma cells after desipramine treatment. METHODS: The viability of C6 cell was assessed by MTT test. The early events of the apopt osis were measured by flow cytometry using annexinV / prop ium iodide (PI) double staining method. RESULTS: Desipramine (5-20 μmol·L -1 ) possessed inhibitory effects on C6 cell pro liferation in a concentration-dependent manner and produced synergetic antiprol iferative effects with C2-ceramide.The proliferation inhibition of desipramine was significantly attenuated by fumonisin B1 (10 μmol·L -1 ) pretreatment for 18 h. After exposure to desipramine ( 20 μmol·L -1 ) for 24 h, C6 g l ioma cells would undergo the early cell apoptosis (13.1 %) which was not a ffected by fumonisin B1 (10 μmol·L -1 ). CONCLUSION: The antidepressant agent desipramine could produce antiproliferative effect on C 6 glioma cell partially through increase of de novo ceramide synthesis.