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.
复制标题
DOI：
10.18632/oncotarget.2640
复制
发表时间：
2014-12-15
期刊：
影响因子：
--
通讯作者：
Jimi E
中科院分区：
文献类型：
--
作者：
Tada Y;Kokabu S;Sugiyama G;Nakatomi C;Aoki K;Fukushima H;Osawa K;Sugamori Y;Ohya K;Okamoto M;Fujikawa T;Itai A;Matsuo K;Watanabe S;Jimi E
口腔鳞状细胞癌（OSCC）细胞显示显著增强的核因子-κB（NF-κB）活性，抑制该活性可抑制恶性肿瘤特征。因此，我们评估了IMD-0560（一种新型IκB激酶（IKK）β抑制剂，正在类风湿性关节炎临床试验中评估）对小鼠OSCC细胞系SCCVII骨侵袭的影响。我们在体外使用人OSCC细胞系和SCCVII细胞检测IMD-0560对NF-κB活性和肿瘤侵袭的抑制作用。使用SCCVII细胞侵袭颌骨的小鼠模型，我们评估了IMD-0560对颌骨侵袭、肿瘤生长和体内基质降解的抑制作用。IMD-0560可抑制NF-κB的核转位和IκBα的降解。IMD-0560还通过抑制OSCC细胞中基质金属蛋白酶-9（MMP-9）的产生来抑制侵袭。IMD-0560可保护SCCVII细胞免受骨肉瘤和下颌骨破坏，通过抑制成骨细胞和SCCVII细胞中NF-κB配体受体激活因子（RANKL）表达减少破骨细胞数量，增加SCCVII细胞死亡，并抑制SCCVII细胞中的细胞增殖和MMP-9产生。基于这些结果，IMD-0560可能代表一种新的治疗剂，用于OSCC细胞的骨侵袭。
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.
登录
查看更多内容
影响因子：
4.8
作者：
Nomura, Takeshi;Shibahara, Takahiko;Takano, Nobuo
通讯作者：
Takano, Nobuo
影响因子：
8.7
作者：
Ghosh S;Hayden MS
通讯作者：
Hayden MS
影响因子：
1.9
作者：
Pandey, Manoj;Rao, Latha P.;Das, Shaima R.
通讯作者：
Das, Shaima R.
影响因子：
4.8
作者：
Dai, S;Hirayama, T;Abu-Amer, Y
通讯作者：
Abu-Amer, Y
影响因子：
7.6
作者：
Boyce, B. F.
通讯作者：
Boyce, B. F.