Abstract 1661: Effect of thalidomide and liposomal doxorubicin on human osteoclastogenesis

Abstract

Abstract Background: Thalidomide has been reported capable of inhibiting angiogenesis and growth of multiple myeloma. Liposomal doxorubicin is known to be mainly absorbed and degraded in reticuloendothelial system, especially the monocyte-macrophage lineage. Since osteoclasts (OCs) are derived from precursors of monocyte-macrophage lineage, we aimed to examine the effect of thalidomide, liposomal doxorubicin and their combination on human osteoclastogenesis. Materials and Methods: We isolated CD14+ cells from peripheral blood mononuclear cells of healthy subjects and generated OCs under stimulation with macrophage-colony forming factor and receptor activator of NK-κB ligand. Cell viability, surface CD51/61 expression, and tartrate-resistant acid phosphatase (TRAP) activity were assessed by using MTT, flow cytometry and immunohistochemical staining, respectively. Results: In comparison with control differentiated OCs, combination of thalidomide (purchased from TTY Biopharm, Taiwan) and liposomal doxorubicin (purchased from TTY Biopharm, Taiwan) profoundly inhibited the amount of harvested viable OCs. By treatment with each drug alone, thalidomide increased and liposomal doxorubicin decreased the amount of viable OCs. The expression of osteoclast-specific surface antigen CD51/61 was greatly inhibited by each drug and their combination. Furthermore, the amount of multinucleated TRAP-positive cells characteristics of OCs, was suppressed by each drug and, the mostly, their combination. Elucidation of cellular and molecular mechanisms of action has been undergoing. Conclusion: Thalidomide, liposomal doxorubicin and their combination may effectively inhibit human osteoclastogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1661.