Search results for: Mouse Anti-Human SOCS3 Antibodies
#23274199 2012/12/27 To Up
Humanised antihuman IL-6R antibody with interferon inhibits renal cell carcinoma cell growth in vitro and in vivo through suppressed SOCS3 expression.
Interleukin-6 (IL-6), one of the proinflammatory cytokines, is considered to be one of the factors associated with poor prognosis of patients with renal cell carcinoma (RCC). Suppressor of cytokine signalling-3 (SOCS3) is rapidly up-regulated by IL-6 and a negative regulator of cytokine signalling. SOCS3 not only suppresses cytokine-mediated JAK/STAT signalling, but also sustains MAPK pathways. In our study, among the RCC cell lines, IL-6 mRNA expression was the highest in the 786-O cells, which also showed the highest level of SOCS3 mRNA expression under the condition of interferon stimulation. In contrast, ACHN cells had the lowest expression of both IL-6 and SOCS3 mRNA under the same condition. Our study is undertaken to evaluate the effect of humanised antihuman IL-6 receptor (IL-6R) antibody, which completely neutralises IL-6 activity, in RCC cell proliferation and its effect on signalling pathways. IL-6R antibody, tocilizumab, significantly suppressed cell proliferation in 786-O cells with interferon stimulation. Western blot analysis revealed that the tocilizumab enhanced the interferon-induced phosphorylation of STAT1 and inhibited SOCS3 expression and the phosphorylation of both STAT3 and ERK. In contrast, the IL-6 inhibited STAT1 phosphorylation, enhanced STAT3 phosphorylation and accelerated cell proliferation in ACHN cells. The in vivo effects of combination therapy with tocilizumab and interferon showed significant suppression of 786-O tumour growth in a xenograft model. Morphological observation of the tumours revealed the apoptosis, invasion of inflammatory cells and fibrosis. These findings suggest that combination therapy using an antihuman IL-6R antibody with interferon may represent a novel therapeutic approach for the treatment of RCC.Toshiki Oguro, Kei Ishibashi, Takashi Sugino, Koichi Hashimoto, Shintaro Tomita, Norio Takahashi, Tomohiko Yanagida, Nobuhiro Haga, Ken Aikawa, Tatsuo Suzutani, Osamu Yamaguchi, Yoshiyuki Kojima
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