imd-0354 and Lymphoma--T-Cell

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-κB (NF-κB) has been reported to play roles in lymphoid malignancies, we examined whether inhibition of NF-κB 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-κB, resulting in GC resistance. Taken together, interference of NF-κB activity may have the synergistic effect in combination chemotherapy with GC for treatment against lymphoid malignancies.

Topics: Animals; Benzamides; Blotting, Western; Dexamethasone; Dog Diseases; Dogs; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Lymphocytes; Lymphoma, B-Cell; Lymphoma, T-Cell; NF-kappa B; Receptors, Glucocorticoid; Reverse Transcriptase Polymerase Chain Reaction; Up-Regulation