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

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• 作者：Jing Xu (1)
  Pengjuan Xu (1)
  Zhigui Li (1)
  Lu Xiao (1)
  Zhuo Yang (1)
  
• 关键词：Remifentanil ; Apoptosis ; C6 cells ; GSK ; 3β ; TDZD ; 8 ; MTT ; Hoechst 33342 ; Flow cytometry ; NMDA receptor ; Glioma
• 刊名：Cellular & Molecular Biology Letters
• 出版年：2013
• 出版时间：December 2013
• 年：2013
• 卷：18
• 期：4
• 页码：494-506
• 全文大小：1,118 KB
• 作者单位：Jing Xu (1)
  Pengjuan Xu (1)
  Zhigui Li (1)
  Lu Xiao (1)
  Zhuo Yang (1)
  
  1. College of Medicine, Nankai University, Tianjin, 300071, China
  
• ISSN：1689-1392

文摘

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.