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Epidermal growth factor receptor status and Notch inhibition in non-small cell lung cancer cells

Efstathia Giannopoulou1, Achilleas Nikolakopoulos1, Dimitra Kotsirilou1,2

  • 1Clinical Oncology Laboratory, Division of Oncology, Department of Medicine, University of Patras, Patras Medical School, Rio, 26504, Greece.

Journal of Biomedical Science
|October 27, 2015
PubMed
Abstract

Insights

Gamma-secretase inhibitor DAPT affects non-small cell lung cancer (NSCLC) cell number, but epidermal growth factor (EGF) impacts Notch signaling. Dual inhibition may be promising for NSCLC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • Notch signaling's dual role (oncogene/tumor suppressor) in lung cancer.
  • Notch receptor cleavage by gamma-secretase yields active Notch intracellular domain (NICD).
  • Epidermal growth factor (EGF) is over-expressed in non-small cell lung cancer (NSCLC).

Purpose of the Study:

  • Investigate DAPT's effect (gamma-secretase inhibitor) on NSCLC cells.
  • Determine EGF's impact on Notch signaling in NSCLC.
  • Analyze the interplay between EGF and Notch pathways.

Main Methods:

  • Utilized NSCLC cell lines (H23, A549, H661, HCC827) with varying NICD and EGFR levels.
  • Administered DAPT and assessed its concentration-dependent effects on cell proliferation and death.
  • Evaluated EGF's influence on DAPT-treated cells and NICD levels.

Main Results:

  • DAPT reduced H661 cell numbers dose-dependently; minimal effect on H23/A549; no effect on HCC827 (mutated EGFR).
  • EGF stimulation did not alter DAPT's effect on cell proliferation.
  • EGF prevented DAPT-induced NICD decrease in H23 and H661 cells, suggesting pathway interaction.

Conclusions:

  • Notch cleavage inhibition may not impact cell number in EGFR-mutated NSCLC.
  • EGFR signaling influences Notch signaling, indicating potential for dual inhibition.
  • Combined inhibition of Notch and EGFR pathways shows promise for NSCLC therapy.

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