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

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.