Targeting Inhibitor of NF-κb Kinase Beta (IKKβ) May Represent a Possible Novel Treatment for Endometriosis

Presentation Number: SUN-0039
Date of Presentation: June 22nd, 2014

Ikuko Sawada*1, Kae Hashimoto1, Kenjiro Sawada1, Tomoyuki Fujikawa2, Akiko Itai2 and Tadashi Kimura1
1Osaka Univ Med Schl, Suita-shi, Japan, 2IMMD. Inc., Tokyo, Japan

Abstract

[Background]

Endometriosis is one of common gynecological diseases associated with chronic pelvic pain and infertility and severely compromises women’s quality of life. Mounting evidence have shown that nuclear factor-κB (NF-κB) pathway activates many of the target genes that are critical to the initiation and establishment of endometriosis. Therefore, we evaluated the therapeutic potential of targeting this pathway using a novel IKKβ inhibitor, IMD-0560 (IMMD. Inc. Tokyo, Japan).

[Methods]

Endometriotic stromal cells (ESCs) were isolated from ovarian chocolate cysts in 20 patients who underwent laparoscopic surgeries. The phosphorylation of IκB was confirmed by Western Blot and the expression of nuclear p65 protein was exampled by immunofluorescent analyses. The inhibitory effects of IMD-0560 on ESCs were assessed by in vitro cell proliferation assay (modified MTS assay), in vitro adhesion assay followed by Western Blots of integrins and quantitative ELISA of a representative inflammatory cytokine, interleukin-6 (IL-6).

[Results]

The treatment of tumor necrosing factor-α (TNF-α) induced IκB phosphorylation as well as a nucllear translocation of p65 protein in ESCs. The co-treatment of IMD-0560 almost abolished these effects. The treatment of IMD-0560 inhibited the proliferative and adhesive activities of ESCs followed by the down-regulation of β1-integrin. In addition, IMD-0560 attenuated the production of IL-6 in a dose-dependant manner.

[Discussion]

IMD-0560 significantly suppressed the proliferative, adhesive activities and a cytokine production of endometriotic cells. Targeting IKKβ may be a novel therapeutic option for endometriosis.

 

Nothing to Disclose: IS, KH, KS, TF, AI, TK