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Published on: November 28, 2015
Notch1 induces enhanced expression of Delta-like-1 in the U251MG glioma cell line
Chun-Fa Qian1, Wei Yan, Jun-Xia Zhang
1Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, PR China.
Abstract:
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.
Insights
This study reveals a positive feedback loop between Notch1 and Delta-like-1 (DLL1) in glioma cells. Targeting both Notch1 and DLL1 simultaneously offers a promising therapeutic strategy for glioma treatment.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Cell Signaling
Background:
- The Notch signaling pathway regulates crucial cellular processes like growth, survival, and differentiation.
- Notch1 and Delta-like-1 (DLL1) are frequently overexpressed in gliomas.
- DLL1 downregulation via RNA interference inhibits glioma cell proliferation and induces apoptosis.
Purpose of the Study:
- To investigate the relationship between Notch1 and DLL1 in glioma cells.
- To explore the potential of targeting the Notch1-DLL1 axis for glioma therapy.
Main Methods:
- Utilized Notch1 expression plasmids and Notch1 receptor blockers in U251MG glioma cells.
- Employed RNA interference to down-regulate DLL1 expression.
- Assessed the effects of single and combined treatments on cell apoptosis and proliferation.
Main Results:
- Notch1 expression upregulated DLL1, while blocking Notch1 downregulated DLL1, indicating a positive feedback loop.
- Both DLL1 downregulation and Notch1 receptor blockade inhibited U251MG cell proliferation and induced apoptosis.
- Combined inhibition of DLL1 and Notch1 yielded synergistic effects, surpassing the impact of individual treatments.
Conclusions:
- A positive feedback loop exists between Notch1 and DLL1 in glioma cells.
- The Notch1-DLL1 axis represents a potential combined therapeutic target for glioma treatment.
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