Combined effects of histone deacetylase inhibitor and rituximab on non-Hodgkin's B-lymphoma cells apoptosis.

摘要: Objective The anti-CD20 monoclonal antibody rituximab has shown promising results in the clinical treatment of patients with B-cell non-Hodgkin's lymphoma (B-NHL). However, its therapeutic effect could still be improved. Methods This study examined anti-tumor activity combined histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) CD20-positive B-NHL cell lines, as well primary cells and a murine model. Results combination sensitized to apoptosis synergistic manner, concomitant mitochondrial instability Bcl-2/Bcl-XL downregulation. Particularly Daudi relatively resistant rituximab, these events were associated nuclear factor-κB (NF-κB) inactivation c-Myc degradation. SAHA presented functional complementation through decreasing IKKα/β IκBα phosphorylation, thus preventing NF-κB translocation. In addition, induced cleavage stable inhibitory form caused degradation response caspase-3 activation. More importantly, rituximab-SAHA significantly promoted improved survival time severe immunodeficient mouse model established intravenous injection cells. Conclusion These findings emphasized value targeting signaling pathway therapy. Rituximab conjunction may represent novel strategy treating B-NHL.