title: The role of glycogen synthase kinase-3β in glioma cell apoptosis induced by remifentanil.
abstract: 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.
authors.affiliation: College of Medicine, Nankai University, Tianjin, 300071, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.forename: Pengjuan
authors.initials: P
authors.lastname: Xu
authors.forename: Zhigui
authors.initials: Z
authors.lastname: Li
authors.forename: Lu
authors.initials: L
authors.lastname: Xiao
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D005910:Glioma / Q000188:drug therapy* / Q000201:enzymology*; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D000077208:Remifentanil; D013830:Thiadiazoles / Q000494:pharmacology
chemical_list: C494356:4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione; D000701:Analgesics, Opioid; D010880:Piperidines; D013830:Thiadiazoles; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3; D000077208:Remifentanil