地昔帕明单用和合用替尼泊苷对大鼠脑胶质瘤C6细胞增殖的调控作用

Effect of desipramine alone and in combination with teniposide on proliferation in rat C6 glioma cells

目的 :研究三环类抗抑郁药地昔帕明 (DMI)对脑胶质瘤C6细胞增殖的调控作用 ,并探讨与临床常用治疗脑瘤的化疗药物替尼泊苷 (VM 2 6 )合用的协同效应。方法 :采用MTT比色法测定大鼠脑胶质瘤C6细胞增殖抑制作用和流式细胞术 (FCM)进行细胞周期分析。结果 :DMI (10— 80 μmol/L)对C6细胞的增殖具有明显的抑制作用 ,呈浓度时间依赖关系 ,药物作用 2 4h的IC50 (95 %置信区间 )为 2 0 7(17 3— 2 4 2 ) μmol/L。DMI (2 0 μmol/L)可使G0 -G1期细胞增加 (P <0 0 5 )而S期细胞减少 (P <0 0 5 ) ,G2 期细胞则无改变。不同浓度DMI和VM 2 6合用显示明显协同效应 (Q =0 72 )。结论 :DMI体外对C6细胞增殖具有浓度时间依赖性抑制作用 ,使细胞阻滞于G0 -G1期 ;与VM 2

Purpose:To study the antiproliferative effect of tricyclic antidepressant desipramine(DMI) alone or in combination with chemotherapeutic agent teniposide (VM 26) against rat C6 glioma cells.Methods:Inhibition of proliferation was measured using MTT colorimetric assay and cell cycle distribution was analysed by flow cytometry(FCM). Results:DMI (10—80?μmol/L) suppressed C6 cell proliferation in a concentration and time dependent manner.The IC 50 and 95% confidence interval were 20.7(17.3—24.2)?μmol/L after 24?h treatment with DMI.DMI(20?μmol/L) significantly increased the proportion of G 0—G 1 phase cells, concomitant with a decrease in the proportion of S phase cells. The combined DMI with VM 26 produced significant synergic antiproliferative effect (combination index Q=0.72). Conclusions:The results indicate DMI could lead to inhibition of C6 cell proliferation and arrest in G 0—G 1 phase of cell cycle, and synergize chemotherapeutic action with VM 26 against C6 glioma cells.