Specific inhibition of Notch1 signaling suppresses properties of lung cancer stem cells
- 1 January 2019
- journal article
- research article
- Published by Medknow in Journal of Cancer Research and Therapeutics
- Vol. 15 (7), 1547-1552
- https://doi.org/10.4103/jcrt.jcrt_482_17
Abstract
Objective: Lung cancer is the leading cause of cancer-related death worldwide with a relatively low 5-year relative survival rate of 16%. Novel and efficient therapeutic approach for lung cancer is desperately needed. Materials and Methods: Targeting cancer stem cells (CSCs) provides a promising strategy to eradicate malignancies. The Notch signaling pathway plays an important role in the control of cell fates and developmental processes including CSCs. The function of Notch1 in the regulation of CSCs and whether targeting Notch1 could be a potential therapy for lung cancer were explored in this study. Lung CSCs (LCSCs) were isolated from A549 cells and identified as CD44+/CD24– cells by magnetic-assisted cell sorting, then the putative LCSCs were treated with Notch1 inhibitor and Notch1 small interfering RNAs (siRNAs); the growth and proliferation of LCSCs were investigated to test the effect of Notch1 blocking on the growth and viability of LCSCs. Results: CD44+/CD24– cells isolated from A549 cells possessed stem cell-like properties with high expression of Notch1. Blocking Notch1 by inhibitor DAPT or siRNA both inhibited the growth capacity of LCSCs. Conclusion: Our discovery demonstrated a depression of growth in CD44+/CD24– and A549 cells caused by blockade of Notch signaling pathway. Further studies are needed to demonstrate the detailed effects of Notch1 blocking on the LCSCs. Nevertheless, targeting the Notch pathway has exhibited great potential to be an improved lung cancer treatment.Keywords
This publication has 27 references indexed in Scilit:
- Improving lung cancer survival; time to move onBMC Pulmonary Medicine, 2012
- Notch Signaling Contributes to Lung Cancer Clonogenic Capacity In Vitro but May Be Circumvented in Tumorigenesis In VivoMolecular Cancer Research, 2011
- Alterations of the Notch pathway in lung cancerProceedings of the National Academy of Sciences of the United States of America, 2009
- Notch signaling promotes airway mucous metaplasia and inhibits alveolar developmentDevelopment, 2009
- γ-Secretase Activation of Notch Signaling Regulates the Balance of Proximal and Distal Fates in Progenitor Cells of the Developing LungOnline Journal of Public Health Informatics, 2008
- Bone morphogenetic proteins inhibit the tumorigenic potential of human brain tumour-initiating cellsNature, 2006
- A human colon cancer cell capable of initiating tumour growth in immunodeficient miceNature, 2006
- Ovarian cancer side population defines cells with stem cell-like characteristics and Mullerian Inhibiting Substance responsivenessProceedings of the National Academy of Sciences of the United States of America, 2006
- A Tumorigenic Subpopulation with Stem Cell Properties in MelanomasCancer Research, 2005
- Prospective identification of tumorigenic breast cancer cellsProceedings of the National Academy of Sciences of the United States of America, 2003