The role of glycogen synthase kinase-3β in glioma cell apoptosis induced by remifentanil

Cellular & Molecular Biology Letters

Pengjuan Xu¹  Zhuo Yang¹  Jing Xu¹  Zhigui Li¹  Lu Xiao¹ 

[1] College of Medicine, Nankai University, Tianjin, China$$

关键词: Remifentanil;    Apoptosis;    C6 cells;    GSK-3β;    TDZD-8;    MTT;    Hoechst 33342;    Flow cytometry;    NMDA receptor;    Glioma;   

DOI  :  10.2478/s11658-013-0102-3

学科分类：分子生物学，细胞生物学和基因

来源: Uniwersytet Wroclawski * Wydzial Biotechnologii / University of Wroclaw, Faculty of Biotechnology

【 摘 要 】

The aim of malignant glioma treatment is to inhibit tumor cell proliferation and induce tumor cell apoptosis. Remifentanil is a clinical anesthetic drug that can activate the N-methyl-D-aspartate (NMDA) receptor. NMDA receptor signaling activates glycogen synthase kinase-3β (GSK-3β). Discovered some 32 years ago, GSK-3β was only recently considered as a therapeutic target in cancer treatment. The purpose of this study was to assess whether remifentanil can induce the apoptosis of C6 cells through GSK-3β activation. 3-(4,5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) was used to detect cell viability. Hoechst 33342 staining and flow cytometry were used to detect cell apoptosis. The effect of GSK-3β activation was detected using a GSK-3β activation assay kit and 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8), a potent and selective small molecule inhibitor of GSK-3β. The MTT assay indicated that remifentanil induced C6 cell death in a concentration- and time-dependent manner. Hoechst 33342 staining and flow cytometry showed that remifentanil significantly induced C6 cell apoptosis. The measurement of GSK-3β activation showed that remifentanil increased the cellular level of GSK-3β. All of these toxic effects can be attenuated by treatment with TDZD-8. These results suggest that remifentanil is able to induce C6 cell apoptosis through GSK-3β activation, which provides a basis for its potential use in the treatment of malignant gliomas.

【 授权许可】

Unknown