Anti-interleukin-6 receptor antibody inhibits the progression in human colon carcinoma cells

• Published in: European journal of clinical investigation Vol. 41; no. 3; pp. 277 - 284
• Main Authors: Hsu, Chih-Ping, Chen, Yung-Liang, Huang, Chiu-Chen, Chou, Chih-Chung, Liu, Chia-Ling, Hung, Chih-Hung, Kao, Ting-Yu, Chung, Yuan-Chiang
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.03.2011; Wiley-Blackwell
• Subjects: Analysis of Variance; Biological and medical sciences; Carcinoma - metabolism; Cell Proliferation; Clonogenic growth; Colonic Neoplasms - metabolism; colorectal carcinoma; Disease Progression; Gastroenterology. Liver. Pancreas. Abdomen; General aspects; Humans; interleukin-6; Interleukin-6 - metabolism; invasiveness; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 9 - metabolism; Medical sciences; Phosphatidylinositol 3-Kinases - metabolism; Receptors, Interleukin-6 - antagonists & inhibitors; Receptors, Interleukin-6 - metabolism; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumor Cells, Cultured; Tumor Stem Cell Assay; Tumors; Rectal disease; Prognosis; Interleukin 6 receptor; Growth; Colorectal carcinoma; Colorectal cancer; Metastasis; interleukin-6; Interleukin 6; Colon cancer; Intestinal disease; Evolution; Tumor cell; Human; Antibody; Cytokine; Clonogenic growth; Malignant tumor; Colonic disease; Medicine; invasiveness; Digestive diseases; Inhibitor; Colon carcinoma; Cancer
• ISSN: 0014-2972; 1365-2362
• DOI: 10.1111/j.1365-2362.2010.02405.x

Eur J Clin Invest 2011; 41 (3): 277–284 Background  Interleukin‐6 (IL‐6) promotes proliferation and invasion in colorectal carcinoma, and serum IL‐6 levels are correlated with survival in patients with colorectal carcinoma. In this study, we attempted to clarify the signal pathway downstream of IL‐6 and the role of the IL‐6 receptor complex in terms of the biological effects of clonogenic growth and invasiveness in colorectal carcinoma cells. Materials and methods  IL‐6‐stimulated SW480 cells were treated with IL‐6 receptor neutralization antibody, mitogen‐activated protein kinase (MAPK) inhibitor and phosphatidylinositol 3‐kinase inhibitor, and clonogenic growth and invasiveness were assessed. IL‐6 and IL‐6 receptor‐expressing LoVo cells were also tested the IL‐6 receptor antibody effect. The downstream molecules of the IL‐6‐mediated pathway were also evaluated. Results  IL‐6 effectively enhanced the clonogenicity and invasiveness of SW480; however, these abilities were reversed by treatment with anti‐IL‐6 receptor antibody, and MAPK and PI3K inhibitors exhibited partial ability to reduce these effects. Similar effects were also found in anti‐IL‐6 receptor antibody‐treated LoVo cells in addition of modulating STAT3 pathway. Anti‐IL‐6 receptor antibody also inhibited matrix metalloproteinase‐2 (MMP‐2) and 9 (MMP‐9) expressions in IL‐6‐stimulated SW480. Conclusions  IL‐6 and the IL‐6R complex could induce clonogenic growth and invasiveness by mediating signals in the Ras/MAPK and PI3K/AKt pathways, and the malignant phenotypes might be associated with the production of MMP‐2 and MMP‐9 after IL‐6 stimulation in SW480 cancer cells.