The Pharmacological NF-κB Inhibitor BAY11-7082 Induces Cell Apoptosis and Inhibits the Migration of Human Uveal Melanoma Cells

被引:26
|
作者
Hu, Shuiqing [2 ]
Luo, Qingqiong [2 ]
Cun, Biyun [1 ]
Hu, Dan [2 ]
Ge, Shengfang [1 ]
Fan, Xianqun [1 ]
Chen, Fuxiang [2 ]
机构
[1] Shanghai Jiao Tong Univ, Dept Ophthalmol, Peoples Hosp 9, Sch Med, Shanghai 200011, Peoples R China
[2] Shanghai Jiao Tong Univ, Dept Clin Labs, Peoples Hosp 9, Sch Med, Shanghai 200011, Peoples R China
基金
中国国家自然科学基金;
关键词
uveal melanoma; NF-kappa B; BAY11-7082; apoptosis; cell migration; TRANSCRIPTION FACTOR; THERAPY; CANCER; PROLIFERATION; EXPRESSION; ACTIVATION; ANTITUMOR; PATHWAYS; TARGET; CYCLE;
D O I
10.3390/ijms131215653
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Uveal melanomas are highly metastatic and have high rate of recurrence due to the lack of effective systemic therapy. The identification of important survival pathways in uveal melanomas provides novel therapeutic targets for effective treatment. In the present study, we found that the NF-kappa B signaling pathway was constitutively and highly activated in uveal melanoma cells. Treatment with the pharmacological NF-kappa B specific inhibitor BAY11-7082 markedly decreased the nuclear translocation of NF-kappa B. In a dose-dependent setting, BAY11-7082 inhibited the proliferation and growth of uveal melanoma cells by inducing apoptosis without effect on cell cycle. The migration capacity of uveal melanoma cells was also significantly suppressed by BAY11-7082 treatment. Mechanistically, BAY11-7082 increased the activity of caspase 3 and reduced the expression of anti-apoptotic protein Bcl-2, but did not influence the expression of pro-apoptotic protein Bax. Furthermore, BAY11-7082 induced uveal melanoma cell apoptosis and inhibited xenograft tumor growth in vivo. Collectively, the present study identified NF-kappa B as an important survival signal for uveal melanoma cells and suggested that administration of specific NF-kappa B inhibitor BAY11-7082 could serve as an effective treatment for patients with uveal melanoma.
引用
收藏
页码:15653 / 15667
页数:15
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