Qian Chun-Fa, Yan Wei, Zhang Jun-Xia, Shi Lei, Qian Jin, Fu Zhen, Kang Chun-Sheng, Liu Ning, You Yong-Ping
Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, PR China.
Int J Mol Med. 2009 Oct;24(4):445-51. doi: 10.3892/ijmm_00000251.
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.
Notch信号通路参与细胞生长、存活和分化的协调调节。先前的研究结果表明，Notch1和Delta样1（DLL1）在许多胶质瘤细胞系和原发性人脑胶质瘤中过表达。通过RNA干扰下调DLL1可抑制多种胶质瘤细胞系的增殖并诱导其凋亡。我们的研究表明，Notch1表达质粒在U251MG胶质瘤细胞系中诱导了更多的DLL1表达。相反，阻断Notch1受体会下调DLL1的表达。下调DLL1和阻断Notch1受体均可诱导U251MG细胞凋亡和增殖抑制，且两种处理联合使用产生的效果比单一处理的效果之和更强。这些发现提示Notch1和DLL1之间存在正反馈回路，这可能成为一个有效的联合治疗靶点。
