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The Effects of Interleukin-33 (IL-33) on Osteosarcoma Cell Viability, Apoptosis, and Epithelial-Mesenchymal Transition are Mediated Through the PI3K/AKT Pathway

Shenyu Wang, Gongyin Zhao, Shujie Zhao, Yusen Qiao, Huilin Yang

Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China (mainland)

Med Sci Monit 2020; 26:e920766

DOI: 10.12659/MSM.920766

Available online: 2020-02-22

Published: 2020-04-21

BACKGROUND: Osteosarcoma is the most common primary tumor of bone. Interleukin-33 (IL-33) is a pro-inflammatory cytokine that also participates in tumor progression. This study aimed to investigate the role of IL-33 in human osteosarcoma cell viability, proliferation, apoptosis, and epithelial-mesenchymal transition (EMT) in vitro and the molecular mechanisms involved.
MATERIAL AND METHODS: The normal osteoblast cell line, hFOB 1.19, and the human osteosarcoma cell lines SOSP-9607, SAOS2, MG63, and U2OS were studied. The expression of IL-33 mRNA and protein in human osteosarcoma cell lines were detected using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot, respectively. The effects of IL-33 on human osteosarcoma cell viability, apoptosis, EMT, and the signaling pathways were studied using the MTT assay, flow cytometry, qRT-PCR, and Western blot.
RESULTS: IL-33 was upregulated in human osteosarcoma cell lines, including U2OS cells. The use of an IL-33 gene plasmid promoted osteosarcoma cell viability, inhibited cell apoptosis, increased the expression of Bcl-2, and reduced the expression of Bax. IL-33 reduced the level of E-cadherin and increased the levels of N-cadherin and matrix metalloproteinase-9 (MMP-9) in osteosarcoma cells at the mRNA and protein level. The use of the IL-33 plasmid increased the protein expression levels of p-AKT and the p-AKT/AKT ratio in osteosarcoma cells, and IL-33 siRNA reversed these findings.
CONCLUSIONS: IL-33 was highly expressed in human osteosarcoma cells. Down-regulation of IL-33 reduced cell viability and EMT of osteosarcoma cells, and induced cell apoptosis through activation of the PI3K/AKT signaling pathway.

Keywords: Apoptosis, Cell Proliferation, Epithelial-mesenchymal transition, Osteosarcoma