1. Academic Validation
  2. The novel IκB kinase β inhibitor IMD-0560 prevents bone invasion by oral squamous cell carcinoma

The novel IκB kinase β inhibitor IMD-0560 prevents bone invasion by oral squamous cell carcinoma

  • Oncotarget. 2014 Dec 15;5(23):12317-30. doi: 10.18632/oncotarget.2640.
Yukiyo Tada 1 Shoichiro Kokabu 2 Goro Sugiyama 2 Chihiro Nakatomi 2 Kazuhiro Aoki 3 Hidefumi Fukushima 4 Kenji Osawa 5 Yasutaka Sugamori 3 Keiichi Ohya 3 Masato Okamoto 6 Tomoyuki Fujikawa 7 Akiko Itai 7 Kou Matsuo 8 Seiji Watanabe 9 Eijiro Jimi 10
Affiliations

Affiliations

  • 1 Division of Molecular Signaling and Biochemistry, Department of Health Promotion, Kyushu Dental University, Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka, Japan. Division of Dental Anesthesiology, Department of Control of Physical Functions, Kyushu Dental University, Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka, Japan.
  • 2 Division of Molecular Signaling and Biochemistry, Department of Health Promotion, Kyushu Dental University, Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka, Japan.
  • 3 Section of Pharmacology, Department of Bio-Matrix, Graduate School, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Tokyo, Japan.
  • 4 Department of Physiological Sciences and Molecular Biology, Fukuoka Dental College, Fukuoka, Tamura, Sawara-ku, Fukuoka, Japan.
  • 5 Division of Pathophysiology, Research Center for Genomic Medicine, Saitama Medical University, Yamane, Hidaka-shi, Saitama, Japan.
  • 6 Department of Advanced Immunotherapeutics, Kitasato University School of Pharmacy, Shirokane, Minato-ku, Tokyo, Japan.
  • 7 Institute of Medical Molecular Design Inc (IMMD Inc), Hongo, Bunkyo-ku, Tokyo, Japan.
  • 8 Division of Oral Pathology, Department of Health Promotion, Kyushu Dental University, Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka, Japan.
  • 9 Division of Dental Anesthesiology, Department of Control of Physical Functions, Kyushu Dental University, Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka, Japan.
  • 10 Division of Molecular Signaling and Biochemistry, Department of Health Promotion, Kyushu Dental University, Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka, Japan. Center for Oral Biological Research, Kyushu Dental University, Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka, Japan.
Abstract

Oral squamous cell carcinoma (OSCC) cells display significantly augmented nuclear factor-κB (NF-κB) activity, and inhibiting this activity suppresses malignant tumor characteristics. Thus, we evaluated the effect of IMD-0560, a novel inhibitor of IκB kinase (IKK) β that is under assessment in a clinical trial of rheumatoid arthritis, on bone invasion by the mouse OSCC cell line SCCVII. We examined the inhibitory effects of IMD-0560 on NF-κB activity and tumor invasion using human OSCC cell lines and SCCVII cells in vitro. Using a mouse model of jaw bone invasion by SCCVII cells, we assessed the inhibitory effect of IMD-0560 on jaw bone invasion, tumor growth, and matrix degradation in vivo. IMD-0560 suppressed the nuclear translocation of NF-κB and the degradation of IκBα in OSCC cells. IMD-0560 also inhibited invasion by suppressing matrix metalloproteinase-9 (MMP-9) production in OSCC cells. IMD-0560 protected against zygoma and mandible destruction by SCCVII cells, reduced the number of osteoclasts by inhibiting receptor activator of NF-κB ligand (RANKL) expression in osteoblastic cells and SCCVII cells, increased SCCVII cell death and suppressed cell proliferation and MMP-9 production in SCCVII cells. Based on these results, IMD-0560 may represent a new therapeutic agent for bone invasion by OSCC cells.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-105661
    98.73%, IκB Kinase β抑制剂
    IKK