Specific inhibition of Notch1 signaling suppresses properties of lung cancer stem cells

J Cancer Res Ther. 2019;15(7):1547-1552. doi: 10.4103/jcrt.JCRT_482_17.


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: CD24; CD44; Notch1; lung cancer stem cells; siRNA.

MeSH terms

  • Biomarkers
  • CD24 Antigen / metabolism
  • Cell Cycle / drug effects
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Diamines / pharmacology
  • Humans
  • Hyaluronan Receptors / metabolism
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / metabolism*
  • RNA Interference
  • RNA, Small Interfering / genetics
  • Receptor, Notch1 / genetics*
  • Receptor, Notch1 / metabolism
  • Signal Transduction* / drug effects
  • Thiazoles / pharmacology


  • 24-diamino-5-phenylthiazole
  • Biomarkers
  • CD24 Antigen
  • CD24 protein, human
  • CD44 protein, human
  • Diamines
  • Hyaluronan Receptors
  • NOTCH1 protein, human
  • RNA, Small Interfering
  • Receptor, Notch1
  • Thiazoles