- 作者: Efstathia Giannopoulou, Achilleas Nikolakopoulos, Dimitra Kotsirilou, Angeliki Lampropoulou, Sofia Raftopoulou, Evangelia Papadimitriou, Achilleas D. Theocharis, Thomas Makatsoris, Konstantinos Fasseas, Haralabos P. Kalofonos
- 作者服務機構: Clinical Oncology Laboratory, Division of Oncology, Department of Medicine, University of Patras, Patras Medical School, Rio , Greece
- 中文摘要: --
- 英文摘要:
Background:
Notch may behave as an oncogene or a tumor suppressor gene in lung cancer cells. Notch receptor undergoes cleavage by enzymes, including γ-secretase, generating the active Notch intracellular domain (NICD). The aim of the present study was to investigate the effect of DAPT, a γ-secretase inhibitor, in non-small cell lung cancer (NSCLC) cells, as well as the impact of epidermal growth factor (EGF) that is over-expressed by NSCLC cells, on Notch signaling. H23, A549, H661 and HCC827 human NSCLC cell lines were used, expressing various NICD and EGF receptor (EGFR) protein levels.
Results:
DAPT decreased the number of H661 cells in a concentration-dependent manner, while it had a small effect on H23 and A549 cells and no effect on HCC827 cells that carry mutated EGFR. Notch inhibition did not affect the stimulatory effect of EGF on cell proliferation, while EGF prevented DAPT-induced NICD decrease in H23 and H661 cells. The type of cell death induced by DAPT seems to depend on the cell type.
Conclusions:
Our data indicate that inhibition of Notch cleavage may not affect cell number in the presence of EGFR mutations and that EGFR may affect Notch signalling suggesting that a dual inhibition of these pathways might be promising in NSCLC. - 中文關鍵字: --
- 英文關鍵字: Notch intracellular domain; Epidermal growth factor receptor; Non-small cell lung cancer cells; Apoptosis; Autophagy; Cell cycle arrest