ABSTRACT: Many studies show the Notch signaling is involved in the pathogenesis of multiple myeloma (MM). This study aimed to explore the effect of Notch signaling on the survival of MM cells. The γ-secretase inhibitor LY-411575 and human MM cell lines, including OPM-2, LP-1, and U266, were used in the study. And blood samples from healthy volunteers were also used as the control comparison. The expression of Hes1 expression was examined by quantitative real-time polymerase chain reaction. The apoptosis of myeloma cells was determined by flow cytometry. LY-411575 did not have effect on peripheral blood mononuclear cells. Notch signaling was block by the cytotoxic effect of LY-411575, mediated through the target Notch gene Hes1. Proapoptotic Noxa in MM cell lines and primary MM cells was increased by LY-411575 through Hes1. The results showed that the survival of MM cells might succeed by Notch signaling.
Medical Oncology 02/2011; 28(4):1626. · 2.14 Impact Factor