Institute of Biopharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Department of Anesthesiology, Chi-Mei Medical Center, Tainan, Taiwan.
Sci Rep. 2017 Dec 14;7(1):17609. doi: 10.1038/s41598-017-17054-1.
Interleukin (IL)-20 is a proinflammatory cytokine involved in rheumatoid arthritis, atherosclerosis, and osteoporosis. However, the role of IL-20 in hepatocellular carcinoma (HCC) is unclear. We explored the function of IL-20 in HCC. Tumor tissue samples were analyzed the expression of IL-20 and cyclin D1 by using immunohistochemistry staining and quantitative real-time polymerase chain reaction (qRT-PCR) analysis. To examine the role of anti-IL-20 monoclonal antibody (7E) in tumor growth, BALB/c mice was injected with ML-1 cells and treated with 7E. HCC tumor tissue expressed higher levels of IL-20 than did non-tumor tissue. High IL-20 expression in HCC was correlated with poor overall survival (relative risk:>3). IL-20 and cyclin D1 expression were also highly correlated in HCC patient specimens and 3 human HCC cell lines. IL-20 also increased cell proliferation and migration, and it regulated matrix metalloproteinase (MMP)-13, tumor necrosis factor (TNF)-α, cyclin D1, and p21 expression in ML-1 cells. 7E attenuated tumor growth in mice inoculated with ML-1 cells. The expression of cyclin D1, TNF-α, MMP-9, and vascular endothelial growth factor was significantly inhibited after 7E treatment. The findings of this study suggest that IL-20 plays a role in the tumor progression of HCC.
白细胞介素 (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,IL-20 在肝细胞癌 (HCC) 中的作用尚不清楚。我们研究了 IL-20 在 HCC 中的功能。通过免疫组织化学染色和定量实时聚合酶链反应 (qRT-PCR) 分析分析肿瘤组织样本中 IL-20 和细胞周期蛋白 D1 的表达。为了研究抗 IL-20 单克隆抗体 (7E) 在肿瘤生长中的作用,将 BALB/c 小鼠注射 ML-1 细胞并用 7E 处理。HCC 肿瘤组织中 IL-20 的表达水平高于非肿瘤组织。HCC 中高 IL-20 表达与总体生存不良相关(相对风险:>3)。IL-20 和细胞周期蛋白 D1 在 HCC 患者标本和 3 个人 HCC 细胞系中也高度相关。IL-20 还可增加细胞增殖和迁移,并调节 ML-1 细胞中基质金属蛋白酶 (MMP)-13、肿瘤坏死因子 (TNF)-α、细胞周期蛋白 D1 和 p21 的表达。7E 可减弱接种 ML-1 细胞的小鼠肿瘤生长。7E 处理后,细胞周期蛋白 D1、TNF-α、MMP-9 和血管内皮生长因子的表达明显受到抑制。本研究结果表明,IL-20 在 HCC 的肿瘤进展中起作用。