Experimental Study On The Effects Of Apoptosis Induced By Notch Receptors Blocker MW167 In U87 Glioma Cells

Objective Recent findings suggest that Notch signaling is critical for survival and proliferation in glioma and stem cells.In order to provide the molecular mechanism for potential application of Notch receptors blockers in the treatment of human glioma.,the study was performed to explore the effect of apoptosis induced by Notch receptors blocker MW167 in U87 glioma cell line.Methods The inhibitory effect of MW167 on the proliferation of U87 cells was assayed by MTT in vitro.The Annexin-FITC and PI staining was applied to detect the apoptosis rate of the U87 glioma cells induced by MW167 by flow cytometery.RT-PCR and flow cytometery were employed to determine the intracellular expression levels of. Hes-1(Hairy/Enhancer of Split-1,Hes-1).The expression change of protein.bcl-2(B-cell lymphocytic-leukemia proto-oncogene 2,bcl-2) was examinged by flow cytometery.Results The method of MTT demonstrated MW167 obviously suppressed the proliferation of the U87 glioma cells(P<0.05) in a concentration-dependent manner.The detection of flow cytometery demonstrates MW167 induced apoptosis of the glioma cells (P<0.05) in a concentration-dependent manner.The mRNA and protein levels of Hes-1,a target of Notch activation,were decreased dose-dependently by MW167.Furthermore, MW167 down-regulated bcl-2(B-cell lymphocytic-leukemia proto-oncogene 2,bcl-2) expressions(P<0.05).Conclusion MW167 significantly inhabits the proliferation of the U87 glioma cells and induces its apoptosis via the modulation of Notch signaling systerm,which suggests Notch receptors blockers,such as MW167,may have a potential therapeutic value for the treatment of human glioma.