Constitutive activation of IκB kinase α and NF-κB in prostate cancer cells is inhibited by ibuprofen
Constitutive activation of IκB kinase α and NF-κB in prostate cancer cells is inhibited by ibuprofen
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DOI：
10.1038/sj.onc.1203160
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发表时间：
1999-12-02
期刊：
影响因子：
8
通讯作者：
Price, BD
中科院分区：
文献类型：
--
作者：
Palayoor, ST;Youmell, MY;Price, BD
由Rel/ nf - κ B家族转录因子控制的凋亡通路可能调节细胞对DNA损伤的反应。在此，我们检测了几种前列腺肿瘤细胞系的nf - κ B状态。在雄激素非依赖性前列腺肿瘤细胞PC-3和DU-145中，NF-kappa B的DNA结合活性被组成性激活，I -kappa B- α水平降低，而雄激素敏感性前列腺肿瘤细胞系LNCaP的NF-kappa B水平较低，并在暴露于细胞因子或DNA损伤后上调，同时测量了介导NF-kappa B活化的I -kappa B- α激酶IKK α的活性。在PC-3细胞中，IKK α活性是组成性的，而LNCaP细胞的IKK α活性是由细胞因子激活的。抗炎剂布洛芬抑制PC-3和DU-145细胞NF-kappa B和IKK α的组成性活化，阻断LNCaP细胞NF-kappa B的刺激活化。结果表明，NF-kappa B在激素不敏感的前列腺肿瘤细胞系PC-3和DU-145中被组成性激活，而在激素敏感的LNCaP细胞系中不被激活。NF-kappa B在前列腺肿瘤细胞中的组成性激活可能增加抗凋亡蛋白的表达，从而降低抗肿瘤治疗的有效性，促进恶性表型的发展。
Apoptotic pathways controlled by the Rel/NF-kappa B family of transcription factors may regulate the response of cells to DNA damage. Here, we have examined the NF-kappa B status Of several prostate tumor cell lines. In the androgen-independent prostate tumor cells PC-3 and DU-145, the DNA-binding activity of NF-kappa B was constitutively activated and I kappa B-alpha levels were decreased, In contrast, the androgen-sensitive prostate tumor cell line LNCaP had low levels of NF-kappa B which were upregulated following exposure to cytokines or DNA damage, The activity of the I kappa B-alpha kinase, IKK alpha, which mediates NF-kappa B activation, was also measured. In PC-3 cells, IKK alpha activity was constitutively active, whereas LNCaP cells had minimal IKK alpha activity that was activated by cytokines. The anti-inflammatory agent ibuprofen inhibited the constitutive activation of NF-kappa B and IKK alpha in PC-3 and DU-145 cells, and blocked stimulated activation of NF-kappa B in LNCaP cells. However, ibuprofen did not directly inhibit I kappa B-alpha kinase, The results demonstrate that NF-kappa B is constitutively activated in the hormone-insensitive prostate tumor cell lines PC-3 and DU-145, but not in the hormone responsive LNCaP cell line. The constitutive activation of NF-kappa B in prostate tumor cells may increase expression of anti-apoptotic proteins, thereby decreasing the effectiveness of anti-tumor therapy and contributing to the development of the malignant phenotype.