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抗白细胞介素-20 单克隆抗体可减轻口腔癌炎症并抑制肿瘤生长。

Anti-IL-20 monoclonal antibody alleviates inflammation in oral cancer and suppresses tumor growth.

机构信息

Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan 70428, Taiwan.

出版信息

Mol Cancer Res. 2012 Nov;10(11):1430-9. doi: 10.1158/1541-7786.MCR-12-0276. Epub 2012 Sep 21.

Abstract

Interleukin-20 (IL-20) is a proinflammatory cytokine involved in rheumatoid arthritis, atherosclerosis, and osteoporosis. However, little is known about the role of IL-20 in oral cancer. We explored the function of IL-20 in the tumor progression of oral cancer. IL-20 expression levels in tumorous and nontumorous oral tissue specimens from 40 patients with four different stages oral cancer were analyzed with immunohistochemistry (IHC) staining and quantitative real-time PCR (qRT-PCR). Expression of IL-20 and its receptor subunits was higher in clinical oral tumor tissue than in nontumorous oral tissue. The role of IL-20 was examined in two oral cancer cell lines (OC-3 and OEC-M1). In vitro, IL-20 promoted TNF-α, IL-1β, MCP-1, CCR4, and CXCR4 and increased proliferation, migration, reactive oxygen species (ROS) production, and colony formation of oral cancer cells via activated STAT3 and AKT/JNK/ERK signals. To evaluate the therapeutic potential of anti-IL-20 monoclonal antibody 7E for treating oral cancer, an ex vivo tumor growth model was used. In vivo, 7E reduced tumor growth and inflammation in oral cancer cells. In conclusion, IL-20 promoted oral tumor growth, migration, and tumor-associated inflammation. Therefore, IL-20 may be a novel target for treating oral cancer, and anti-IL-20 monoclonal antibody 7E may be a feasible therapeutic.

摘要

白细胞介素-20(IL-20)是一种促炎细胞因子,参与类风湿关节炎、动脉粥样硬化和骨质疏松症的发生。然而,关于 IL-20 在口腔癌中的作用知之甚少。我们探讨了 IL-20 在口腔癌肿瘤进展中的作用。通过免疫组织化学(IHC)染色和实时定量 PCR(qRT-PCR)分析了 40 例不同阶段口腔癌患者肿瘤和非肿瘤口腔组织标本中 IL-20 的表达水平。IL-20 和其受体亚基在临床口腔肿瘤组织中的表达高于非肿瘤口腔组织。在两种口腔癌细胞系(OC-3 和 OEC-M1)中检查了 IL-20 的作用。在体外,IL-20 通过激活 STAT3 和 AKT/JNK/ERK 信号促进 TNF-α、IL-1β、MCP-1、CCR4 和 CXCR4 的表达,增加口腔癌细胞的增殖、迁移、活性氧(ROS)产生和集落形成。为了评估抗 IL-20 单克隆抗体 7E 治疗口腔癌的治疗潜力,使用了离体肿瘤生长模型。在体内,7E 减少了口腔癌细胞的肿瘤生长和炎症。总之,IL-20 促进了口腔肿瘤的生长、迁移和肿瘤相关炎症。因此,IL-20 可能是治疗口腔癌的新靶点,抗 IL-20 单克隆抗体 7E 可能是一种可行的治疗方法。

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