›› 2012, Vol. 32 ›› Issue (8): 1024-.doi: 10.3969/j.issn.1674-8115.2012.08.014

• Original article (Basic research) • Previous Articles     Next Articles

Influence of blocking Notch signaling pathway by γ-secretase inhibitor on proliferation of lung adenocarcinoma A549 cells

ZHOU Min1,2, FAN Zhi-wen1, HAN Rui-chao1   

  1. 1.Department of Respiratory Medicine, the Third People´s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 201900, China；2.Department of Respiratory Medicine, Jinshan Branch of the Sixth People´s Hospital, Shanghai Jiaotong University, Shanghai 201500, China
  • Online:2012-08-28 Published:2012-08-29
  • Supported by:

    Shanghai Education Committee Foundation, 11YZ44；Shanghai Jinshan District Science and Technology Innovation Foundation, 2011-3-06

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Abstract:

Objective To observe the influence of blocking Notch signaling pathway by γ-secretase inhibitor MW167 on the proliferation of lung adenocarcinoma A549 cells. Methods Lung adenocarcinoma A549 cells were cultured in vitro under normoxic condition, and the expression of Notch receptor subtypes was detected by Western blotting and RT-PCR. Under normoxic condition, lung adenocarcinoma A549 cells were treated with different concentrations (5, 10 and 20 μmol/L) of MW167 (treatment groups). Forty-eight hours after treatment, the expression of Notch1 protein was determined by Western blotting, the expression of Notch signaling pathway downstream gene HES1mRNA was detected by RT-PCR, and the influence of MW167 on cell proliferation was determined by MTT. Besides, DMSO control groups of corresponding concentrations were established. Results Notch1-4 subtypes were expressed in A549 cells. Compared with control groups, the expression of Notch1 protein was higher (P<0.05) and that of HES1 mRNA was lower (P<0.05) in treatment groups 48 h after treatment, and the inhibition rate of HES1 mRNA expression increased with MW167 concentrations (r=0.927, P<0.01). The absorbance of each treatment group was higher than that of each control group (P<0.05), and the cell proliferation rates increased with MW167 concentrations (r=0.904, P<0.01). Conclusion Under normoxic condition, MW167 may block Notch signaling pathway and promote proliferation of A549 cells. Notch1 signaling pathway may play a tumor suppressing role in A549 cells.

Key words: γ-secretase inhibitor, Notch signal, lung adenocarcinomaNotch