Prednisolone and chlormethine inhibit multiple myeloma through inhibition of Notch/NF-κB-mediated angiogenesis

In multiple myeloma, bone marrow angiogenesis parallels tumor progression and correlates with disease activity. In this study, we examined the effects of prednisolone and chlormethine on myeloma cell viability, apoptosis and the expression of angiogenic factors. Human umbilical vein endothelial cells (HUVECs) and RPMI 8226 cells were treated with various concentrations of prednisolone and chlormethine at different time points. CCK-8 was used to analyze cell viability, and cell cycle and apoptosis were analyzed by flow cytometry. Real-time PCR and Western blot were used to measure the expression of angiogenic factors. Administration of prednisolone and chlormethine alone or combination inhibited cell viability, arrested cell cycle and induced cell apoptosis of HUVECs and RPMI 8226 cells. Treatment of HUVECs and RPMI 8226 cells with prednisolone and chlormethine alone or combination caused a decrease of angiogenic factors, such as Notch-1, NF-kappa Bp65, VEGF, bFGF, MMP-2 and MMP-9. Prednisolone and chlormethine inhibit multiple myeloma angiogenesis by inhibiting Notch/NF-kappa B signaling pathway. Notch/NF-kappa B signaling pathway can be a target for the treatment of multiple myeloma.