Notch1 induces enhanced expression of Delta-like-1 in the U251MG glioma cell line.

The Notch signaling pathway takes part in coordinated regulation of cell growth, survival and differentiation. Previous findings have shown that Notch1 and Delta-like-1 (DLL1) are overexpressed in many glioma cell lines and primary human gliomas. Down-regulation of DLL1 by RNA interference inhibits proliferation and induces apoptosis in multiple glioma cell lines. Our studies showed that Notch1 expression plasmid induced more expression of DLL1 in the U251MG glioma cell line. Adversely, blocking Notch1 receptors down-regulated the expression of DLL1. Both down-regulating DLL1 and blocking Notch1 receptors induced U251MG cell apoptosis and proliferation inhibition, and combining the two treatments produced stronger effects than the sum of a single treatment. These findings suggest a positive feedback loop between Notch1 and DLL1, which may become an effective combined therapeutic target.