Overexpression of interleukin-18 protein reduces viability and induces apoptosis of tongue squamous cell carcinoma cells by activation of glycogen synthase kinase-3β signaling

Liu,Weiwei; Hu,Min; Wang,Yumei; Sun,Baozhen; Guo,Yu; Xu,Zhimin; Li,Jia; Han,Bing

doi:10.3892/or.2015.3724

Overexpression of interleukin-18 protein reduces viability and induces apoptosis of tongue squamous cell carcinoma cells by activation of glycogen synthase kinase-3β signaling

Authors:
- Weiwei Liu
- Min Hu
- Yumei Wang
- Baozhen Sun
- Yu Guo
- Zhimin Xu
- Jia Li
- Bing Han
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Affiliations: Department of Oral and Maxillofacial Surgery, School of Stomatology, Jilin University, Changchun 130021, P.R. China, Department of Orthodontics, School of Stomatology, Jilin University, Changchun 130021, P.R. China, Department of Hepatobiliary and Pancreatic Surgery, China-Japan Union Hospital, Jilin University, Changchun 130021, P.R. China
Published online on: January 15, 2015 https://doi.org/10.3892/or.2015.3724
Pages: 1049-1056
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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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.

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