Antitumor effects of interleukin‐6 (IL‐6)/interleukin‐6 receptor (IL‐6R) signaling pathway inhibition in clear cell carcinoma of the ovary

In this study, we aim to clarify whether IL‐6/IL‐6R mediated signaling pathway could have clinical relations with CCC and to evaluate inhibitory effects of the pathway on CCC carcinogenesis. A total of 84 CCC cases collected from primary surgical specimens were evaluated by the immunohistochemical analysis for IL‐6R and phosphorylated Stat3 (pStat3), and we found that high IL‐6R expression correlated with poor patient survival both by the univariate and multivariate analyses, suggesting that IL‐6/IL‐6R signaling pathway could be implicated in the progression of CCC. We further investigated the effects of IL‐6/IL‐6R mediated signaling pathway inhibition either by IL‐6R small interfering RNA (siRNA) approach or humanized anti‐human IL‐6R antibody (tocilizumab) in CCC. Inhibition of endogenous IL‐6R including tocilizumab in CCC cells did reduce cell invasion ability and restored their response to cytotoxic reagent. These data suggest that IL‐6/IL‐6R signaling pathway could act on CCC cells to enhance invasion and chemoresistance and, therefore, targeting IL‐6/IL‐6R mediated signaling pathway could be a promising therapeutic strategy for CCC. © 2015 Wiley Periodicals, Inc.

Source: Molecular Carcinogenesis - April 10, 2015 Category: Molecular Biology Authors: Nozomu Yanaihara, Yukihiro Hirata, Noriko Yamaguchi, Yukiko Noguchi, Misato Saito, Chie Nagata, Satoshi Takakura, Kyosuke Yamada, Aikou Okamoto Tags: Research Article Source Type: research