三苯氧胺类药物和地塞米松对恶性神经胶质瘤细胞呼吸的体外作用。

The in vitro effects of tricyclic drugs and dexamethasone on cellular respiration of malignant glioma.

机构信息

Cellular and Molecular Neuro-oncology Group, Institute of Biomedical and Biomolecular Sciences, School of Pharmacy and Biomedical Sciences, White Swan Road, University of Portsmouth, Portsmouth, Hampshire PO1 2DT, UK.

出版信息

Anticancer Res. 2010 Feb;30(2):391-7.

PMID:20332444

Abstract

BACKGROUND

In this investigation the effects of tricyclic drugs on cellular respiration were studied using the anaplastic astrocytoma cell line IPSB-18 by use of a Clark-type oxygen electrode which measured changes in cellular respiration rate (oxygen consumption), in a dose-response assay.

MATERIALS AND METHODS

The drugs investigated were clomipramine, norclomipramine, amitriptyline and doxepin. In addition, the combined effects of dexamethasone and clomipramine on cellular respiration were investigated.

RESULTS

It was established that at lower concentrations (0.14 mM-0.5 mM) amitriptyline was the most potent inhibitor of cellular respiration. Previous studies have indicated that inhibition of cellular respiration is considered an indicator of apoptosis. Overall, it appeared that clomipramine and its metabolite norclomipramine were the most potent inhibitors of cellular respiration in glioma cells over the concentration range 0.5-0.9 mM. Dexamethasone was able to induce inhibition of cellular respiration both alone in glioma cells, and in combination with clomipramine, where it had an additive or synergistic effect, thereby increasing cell death.

CONCLUSION

The extensive research currently ongoing and previously reported regarding the use of clomipramine as a potential antineoplastic agent aimed at targeting the mitochondria of gliomas is promising.

摘要

背景

本研究采用Clark 型氧电极，通过剂量反应试验，检测细胞耗氧率（细胞呼吸速率）的变化，研究三环类药物对增生性星形细胞瘤 IPSB-18 细胞系的细胞呼吸的影响。

材料与方法

研究的药物为氯米帕明、去甲氯米帕明、阿米替林和多塞平。此外，还研究了地塞米松与氯米帕明联合对细胞呼吸的影响。

结果

结果表明，在较低浓度（0.14mM-0.5mM）时，阿米替林对细胞呼吸的抑制作用最强。先前的研究表明，细胞呼吸抑制被认为是细胞凋亡的一个指标。总的来说，在 0.5-0.9mM 浓度范围内，氯米帕明及其代谢产物去甲氯米帕明似乎是对神经胶质瘤细胞呼吸抑制作用最强的三环类药物。地塞米松单独或与氯米帕明联合使用时，均可诱导细胞呼吸抑制，具有相加或协同作用，从而增加细胞死亡。