Anti-IL-20 monoclonal antibody inhibited tumor growth in hepatocellular carcinoma

被引:10
作者
Chiu, Yi-Shu [1 ]
Hsing, Chung-Hsi [3 ]
Li, Chien-Feng [4 ,5 ,6 ]
Lee, Chon-Yee [2 ]
Hsu, Yu-Hsiang [7 ,8 ]
Chang, Ming-Shi [1 ,2 ]
机构
[1] Natl Cheng Kung Univ, Inst Biopharmaceut Sci, Coll Med, Tainan, Taiwan
[2] Natl Cheng Kung Univ, Dept Biochem & Mol Biol, Coll Med, Tainan, Taiwan
[3] Chi Mei Med Ctr, Dept Anesthesiol, Tainan, Taiwan
[4] Chi Mei Med Ctr, Dept Pathol, Tainan, Taiwan
[5] Natl Hlth Res Inst, Natl Inst Canc Res, Tainan, Taiwan
[6] Southern Taiwan Univ Sci & Technol, Dept Biotechnol, Tainan, Taiwan
[7] Natl Cheng Kung Univ, Inst Clin Med, Coll Med, Tainan, Taiwan
[8] Natl Cheng Kung Univ, Natl Cheng Kung Univ Hosp, Coll Med, Res Ctr Clin Med, Tainan, Taiwan
关键词
CANCER; INTERLEUKIN-19; INFLAMMATION; CYTOKINE; IL-20;
D O I
10.1038/s41598-017-17054-1
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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)-alpha, cyclin D1, and p21(WAF1) expression in ML-1 cells. 7E attenuated tumor growth in mice inoculated with ML-1 cells. The expression of cyclin D1, TNF-alpha, 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.
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页数:10
相关论文
共 23 条
[11]   The STAT3 inhibitor NSC 74859 is effective in hepatocellular cancers with disrupted TGF-β signaling [J].
Lin, L. ;
Amin, R. ;
Gallicano, G. I. ;
Glasgow, E. ;
Jogunoori, W. ;
Jessup, J. M. ;
Zasloff, M. ;
Marshall, J. L. ;
Shetty, K. ;
Johnson, L. ;
Mishra, L. ;
He, A. R. .
ONCOGENE, 2009, 28 (07) :961-972
[12]  
MCCLELLAND RA, 1990, CANCER RES, V50, P3545
[13]   CYCLIN-D AND ONCOGENESIS [J].
MOTOKURA, T ;
ARNOLD, A .
CURRENT OPINION IN GENETICS & DEVELOPMENT, 1993, 3 (01) :5-10
[14]   Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production [J].
Naugler, Willscott E. ;
Sakurai, Toshiharu ;
Kim, Sunhwa ;
Maeda, Shin ;
Kim, KyoungHyun ;
Elsharkawy, Ahmed M. ;
Karin, Michael .
SCIENCE, 2007, 317 (5834) :121-124
[15]   Interleukin-10 and related cytokines and receptors [J].
Pestka, S ;
Krause, CD ;
Sarkar, D ;
Walter, MR ;
Shi, YF ;
Fisher, PB .
ANNUAL REVIEW OF IMMUNOLOGY, 2004, 22 :929-979
[16]  
Scott KA, 2003, MOL CANCER THER, V2, P445
[17]   Functions of cyclin D1 as an oncogene and regulation of cyclin D1 expression [J].
Tashiro, Etsu ;
Tsuchiya, Ayako ;
Imoto, Masaya .
CANCER SCIENCE, 2007, 98 (05) :629-635
[18]   Molecular targeted therapy for hepatocellular carcinoma [J].
Thomas, Melanie .
JOURNAL OF GASTROENTEROLOGY, 2009, 44 :136-141
[19]   IL-20 is an arteriogenic cytokine that remodels collateral networks and improves functions of ischemic hind limbs [J].
Tritsaris, Katerina ;
Myren, Maja ;
Ditlev, Sisse B. ;
Hubschmann, Martin V. ;
van der Blom, Ida ;
Hansen, Anker Jon ;
Olsen, Uffe B. ;
Cao, Renhai ;
Zhang, Junhang ;
Jia, Tanghong ;
Wahlberg, Eric ;
Dissing, Steen ;
Cao, Yihai .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (39) :15364-15369
[20]   IL-20: biological functions and clinical implications [J].
Wei, Chi-Chen ;
Hsu, Yu-Hsiang ;
Li, Hsing-Hui ;
Wang, Yo-Ching ;
Hsieh, Mei-Yi ;
Chen, Wei-Yu ;
Hsing, Chung-Hsi ;
Chang, Ming-Shi .
JOURNAL OF BIOMEDICAL SCIENCE, 2006, 13 (05) :601-612