A novel NF-κB inhibitor improves glucocorticoid sensitivity of canine neoplastic lymphoid cells by up-regulating expression of glucocorticoid receptors
A novel NF-κB inhibitor improves glucocorticoid sensitivity of canine neoplastic lymphoid cells by up-regulating expression of glucocorticoid receptors
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DOI：
10.1016/j.rvsc.2010.03.017
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发表时间：
2010-12-01
影响因子：
2.4
通讯作者：
Matsuda, H.
中科院分区：
文献类型：
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作者：
Matsuda, A.;Tanaka, A.;Matsuda, H.
淋巴肿瘤包括淋巴瘤和白血病是狗最致命的疾病之一。糖皮质激素（GC）可以很好地治疗许多淋巴细胞恶性肿瘤；然而，有时会发生GC抗性，其机制尚不清楚。由于核因子κ B （nf - κ B）的组成性激活在淋巴细胞恶性肿瘤中发挥作用，我们研究了用合成抑制剂IMD-0354抑制nf - κ B活性是否会影响犬肿瘤淋巴样细胞CL-1和GL-1的GC敏感性。地塞米松未能抑制这些细胞的增殖，其中发现糖皮质激素受体（GR）低表达。在IMD-0354的存在下。GR在CL-1和GL-1中的表达升高，表明地塞米松抑制了它们的增殖。这些结果表明，NF-kappa B的自发激活可能下调了GR的表达，从而产生GC抗性。综上所述，干扰NF-kappa B活性可能在联合化疗与GC治疗淋巴细胞恶性肿瘤中具有协同作用。(C) 2010 Elsevier Ltd.版权所有。
Lymphoid neoplasms including lymphoma and leukemia are one of the most life-threatening disorders in dogs. Many lymphoid malignancies are well-treated with glucocorticoid (GC); however, GC resistance sometimes develops and its mechanism remains uncertain. Since constitutive activation of nuclear factor-kappa B (NF-kappa B) has been reported to play roles in lymphoid malignancies, we examined whether inhibition of NF-kappa B activity with a synthetic inhibitor IMD-0354 affected GC sensitivity of canine neoplastic lymphoid cells, CL-1 and GL-1. Dexamethasone failed to inhibit proliferation of these cells, in which low expression of glucocorticoid receptors (GR) was identified. In the presence of IMD-0354. GR expressions in CL-1 and GL-1 were increased, consequently dexamethasone inhibited their proliferation. These results indicated that GR expression might be down-regulated by spontaneous activation of NF-kappa B, resulting in GC resistance. Taken together, interference of NF-kappa B activity may have the synergistic effect in combination chemotherapy with GC for treatment against lymphoid malignancies. (C) 2010 Elsevier Ltd. All rights reserved.