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


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.
Department of Medical Laboratory Science and Biotechnology, Yuanpei University, Hsin-Chu City, Taiwan.
Chih-Ping
CP
Hsu
Yung-Liang
YL
Chen
Chiu-Chen
CC
Huang
Chih-Chung
CC
Chou
Chia-Ling
CL
Liu
Chih-Hung
CH
Hung
Ting-Yu
TY
Kao
Yuan-Chiang
YC
Chung
D000704:Analysis of Variance; D002277:Carcinoma / Q000378:metabolism*; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000378:metabolism*; D018450:Disease Progression; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D019869:Phosphatidylinositol 3-Kinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9