title: Overexpression of interleukin-18 protein reduces viability and induces apoptosis of tongue squamous cell carcinoma cells by activation of glycogen synthase kinase-3β signaling.
abstract: The aim of this study was to investigate the effects of interleukin-18 (IL-18) expression on regulating the viability and apoptosis of tongue squamous cell carcinoma (TSCC) cells in vitro and examine the underlying molecular events. Human IL-18 cDNA was cloned into the vector pcDNA3.1 (+) and transfected into CRL-1623™ cells. Quantitative reverse transcription-PCR (RT-qPCR), western blot analysis, immunofluorescence, cell viability MTT assay, flow cytometric Annexin V/propidium iodide (PI), Giemsa staining, and caspase-3 activity assay were performed. The data showed that overexpression of IL-18 protein reduced TSCC cell viability by inducing apoptosis. Compared with cells transfected with the control vector, IL-18 expression activated caspase-3, -7, and -9 by inducing their cleavage and increased the expression of interferon (IFN)-γ and cytochrome c mRNA, but reduced cyclin D1 and A1 expression in TSCC cells. IL-18 expression upregulated the expression and phosphorylation of glycogen synthase kinase (GSK)-3β protein in CRL1623 cells, whereas the selective GSK-3β inhibitor kenpaullone antagonized the effects of IL-18 protein on TSCC cells in vitro. The results indicated that IL-18 played an important role in the inhibition of TSCC cell growth and may be further investigated as a novel therapeutic target against TSCC.
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Stomatology, Jilin University, Changchun 130021, P.R. China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Orthodontics, School of Stomatology, Jilin University, Changchun 130021, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Hu
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Stomatology, Jilin University, Changchun 130021, P.R. China.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, China-Japan Union Hospital, Jilin University, Changchun 130021, P.R. China.
authors.forename: Baozhen
authors.initials: B
authors.lastname: Sun
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Stomatology, Jilin University, Changchun 130021, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Stomatology, Jilin University, Changchun 130021, P.R. China.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Stomatology, Jilin University, Changchun 130021, P.R. China.
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Stomatology, Jilin University, Changchun 130021, P.R. China.
authors.forename: Bing
authors.initials: B
authors.lastname: Han
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D002470:Cell Survival / Q000502:physiology; D004789:Enzyme Activation / Q000502:physiology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D020382:Interleukin-18 / Q000096:biosynthesis*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D014062:Tongue Neoplasms / Q000378:metabolism / Q000473:pathology*; D014162:Transfection
chemical_list: C000589760:IL18 protein, human; D020382:Interleukin-18; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3