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

Authors


Yuan-Chiang Chung MD, PhD, Department of Surgery, Hsin-Chu General Hospital, No. 25, Lane 442, Sec. 1, Chin-Kuo Rd, Hsin-Chu City 300, Taiwan. Tel.: +886 3 532 6151#8660; fax: +886 3 532 4584; e-mail: young@hch.gov.tw; hch21001@hch.doh.gov.tw

Abstract

Eur J Clin Invest 2011; 41 (3): 277–284

Abstract

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.

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