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

Yukiyo Tada, Shoichiro Kokabu, Goro Sugiyama, Chihiro Nakatomi, Kazuhiro Aoki, Hidefumi Fukushima, Kenji Osawa, Yasutaka Sugamori, Keiichi Ohya, Masato Okamoto, Tomoyuki Fujikawa, Akiko Itai, Kou Matsuo, Seiji Watanabe, Eijiro Jimi

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

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 IκBa 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.

Original languageEnglish
Pages (from-to)12317-12330
Number of pages14
JournalOncotarget
Volume5
Issue number23
DOIs
Publication statusPublished - 2014

Keywords

  • Bone invasion
  • IMD-0560
  • NF-κB
  • Oral squamous cell carcinoma

ASJC Scopus subject areas

  • Oncology

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