地昔帕明对脑胶质瘤C6细胞的增殖抑制和凋亡诱导作用

目的研究地昔帕明（ＤＭＩ）对大鼠脑胶质瘤Ｃ６的增殖抑制和凋亡诱导作用，为三环类抗抑郁药作为肿瘤辅助治疗提供新的理论和实验依据。方法用ＭＴＴ比色法测定Ｃ６细胞活力，用透射电镜、流式细胞术（ＦＣＭ）检测细胞凋亡，用免疫组化法分析ｂｃｌ－２蛋白的表达。结果ＤＭＩ对Ｃ６细胞的增殖具有明显的浓度依赖性抑制作用， ＩＣ５０（ ９５ ％置信区间）为２０．７（１７．３～２４．２）μｍｏｌ·Ｌ－１，细胞阻滞于Ｇ０～Ｇ１期。ＤＭＩ（４０μｍｏｌ·Ｌ－１）使细胞发生典型的凋亡形态改变，ＤＮＡ含量分析显示 Ｇ０峰左侧出现亚二倍体细胞凋亡峰，呈浓度依赖性，蛋白合成抑制剂ＣＨＸ可显著抑制ＤＭＩ诱导的细胞凋亡。同时，ＤＭＩ（１０ μｍｏｌ·Ｌ－１）可下调细胞 ｂｃｌ－２蛋白的表达。结论ＤＭＩ体外对Ｃ６细胞的增殖具浓度依赖性抑制作用，并诱导细胞凋亡。

Effect of desipramine on proliferation inhibition and apoptosis induction in rat glioma C6 cells

AIM　To study the effect of desipramin e (DMI) on proliferation inhibition and apoptosis induction of rat glioma C6 cel ls. METHODS　Cell proliferation w as measured by MTT colorimetric assay and cells undergoing apoptosis were determ ined by electron microscope and flow cytometry. The expression of bcl-2 was eva luated by immunohistochemistry. RESULTS　DMI could result in the c oncentration-dependent inhibition of C6 cell proliferation and lead to arrest i n G0～G1 phase of cell cycle. The value of IC50 and 95% confidence lim its were 20.7(17.3～24.2) μmol*L－1.DMI（40 μmol*L－1）-indu ced apoptosis showed classical apoptotic morphology and the hypodiploid peak ap peared on the histogram of FCM in a concentration-dependent manner, which could be abrogated by cycloheximide(1.8 μmol*L－1). Meanwhile, DMI (10 μmol *L－1) could down-regulate the expression of apoptosis associated gene b cl-2. CONCLUSION　DMI could inhibit cell proliferation in a con centration dependent manner and induce typical apoptosis of C6 cells.