Interleukin‑22 modulates cisplatin sensitivity of osteosarcoma cells by regulating the STAT3 signaling pathway

Li,Zhiqiang; Xu,Renjie; Zhang,Xiangxin; Shen,Jun; Chen,Guangxiang; Zou,Tianming; Yu,Xiao

doi:10.3892/etm.2019.8352

Interleukin‑22 modulates cisplatin sensitivity of osteosarcoma cells by regulating the STAT3 signaling pathway

Authors:
- Zhiqiang Li
- Renjie Xu
- Xiangxin Zhang
- Jun Shen
- Guangxiang Chen
- Tianming Zou
- Xiao Yu
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Affiliations: Department of Orthopedics, Nanjing Medical University Affiliated Suzhou Hospital (Suzhou Municipal Hospital), Suzhou, Jiangsu 215002, P.R. China
Published online on: December 19, 2019 https://doi.org/10.3892/etm.2019.8352
Pages: 1379-1387
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study aimed to investigate the regulatory mechanisms by which interleukin (IL)‑22 regulates cisplatin (DDP) sensitivity in osteosarcoma cells. Firstly, reverse transcription‑quantitative (RT‑q) PCR and western blotting demonstrated that IL‑22 expression was significantly increased in osteosarcoma tissues and cell lines compared with the adjacent normal tissues and the normal osteoblast hFOB1.19 cells. Subsequently, the MG63 osteosarcoma cell line and cisplatin‑resistant MG63/DDP osteosarcoma cell line were treated with different concentrations of cisplatin (2.5, 5.0, 10, 20, 40 and 80 µg/ml), and the half maximal inhibitory concentration (IC50) was calculated based on the MTT assay. The results showed that the IC50 of DDP in MG63/DDP cells was significantly higher than that in MG63 cells. Furthermore, IL‑22 expression was higher in MG63/DDP cells compared with MG63 cells. Subsequently, the effects of IL‑22 downregulation and overexpression on MG63/DDP and MG63 cells were assessed using the MTT assay, flow cytometry, RT‑qPCR and western blotting. The IL‑22 small interfering (si) RNA in MG63/DDP cells significantly decreased the IC50 of DDP and decreased the cell viability of MG63/DDP cells. Furthermore, IL‑22 RNA interference decreased BCl‑2 expression and phosphorylation of STAT3, induced apoptosis, and increased the expression of Bax and cleaved caspase‑3. The IL‑22 overexpression plasmid had opposite effects to the observations in IL‑22 siRNA‑transfected MG63 cells. Overall, the present study indicated that IL‑22 regulated the cell viability and apoptosis of osteosarcoma cells by regulating the activation of the STAT3 signaling pathway and affecting the expression of apoptosis‑associated genes, and thereby mediating the sensitivity of osteosarcoma cells to cisplatin.

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