地昔帕明对脑胶质瘤C6细胞的增殖抑制和凋亡诱导作用  

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

作　　者：祁红[1] 陈红专[1] 冯菊妹[1] 孙玉燕[1] 金正均[1] 

机构地区：[1]上海第二医科大学药理学教研室,上海200025

出　　处：《中国药理学通报》2001年第2期161-164,共4页Chinese Pharmacological Bulletin

基　　金：上海市教委科技发展基金资助课题;No 5990208

摘　　要：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。AIM To study the effect of desipramine (DMI ) on proliferation inhibition and apoptosis induction of rat glioma C6 cells. METH ODS Cell proliferation was measured by MTT col- orimetric assay and cells undergoing apoptosis were determined by electron microscope and flow cytometry. The expression of hcf-2 was evaluated by immunohistochemistry. RESULTS DMI could result in the concentration- dependent inhibition of C6 cell proliferation and lead to arrest in GO - G1 phase of cell cycle. The value of Ica and 95% confidence limits were 20.7(17 .3~24 .2) μmol·L~ 1. DMI(40 μmol· L-l )-induced apoptosis showed classical apoptotic morphology and the hypodiploid peak appeared on the histogram of FCM in a concentration- dependent man ner, 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 hcl-2. CONCLUSION DMI could inhibit cell proliferation in a concentration dependent manner and induce typical apoptosis of C6 cells.

关 键 词：抗抑郁药 地昔帕明 脑胶质瘤 细胞凋亡 细胞增殖 

分 类 号：R739.41[医药卫生—肿瘤] R941.43[医药卫生—临床医学]