A novel NF-kappa B inhibitor improves glucocorticoid sensitivity of canine neoplastic lymphoid cells by up-regulating expression of glucocorticoid receptors

作者：Matsuda A; Tanaka A; Muto S; Ohmori K; Furusaka T; Jung K; Karasawa K; Okamoto N; Oida K; Itai A; Matsuda H^*

来源：Research in Veterinary Science, 2010, 89(3): 378-382.

DOI：10.1016/j.rvsc.2010.03.017

• Glucocorticoid receptor
• IMD-0354
• Lymphoma/leukemia
• NF-kappa B

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.

• 出版日期2010-12
• 单位河北医科大学