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Over-activated Notch-1 protects gastric carcinoma BGC-823 cells from TNFalpha-induced apoptosis

J Yao1, C Qian

  • 1School of Medicine, Taizhou University, Jiaojiang District, Taizhou, Zhejiang 318000, PR China.

Digestive and Liver Disease : Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver
|May 1, 2009
PubMed
Abstract

Insights

Over-activated Notch-1 protects human gastric carcinoma cells from TNFalpha-induced apoptosis by reducing caspase-3 activation. This Notch-1 effect is independent of NF-kappaB signaling in BGC-823 cells.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • The role of Notch-1 in human gastric carcinoma is not well understood.
  • Gastric carcinoma is a common cancer of the digestive tract.

Purpose of the Study:

  • Investigate the effect of Notch-1 activation on TNFalpha-induced apoptosis in human gastric carcinoma BGC-823 cells.
  • Elucidate the molecular mechanism underlying Notch-1's role in gastric cancer cell apoptosis.

Main Methods:

  • Cell viability assessed by MTT assay.
  • Apoptosis detected via flow cytometry.
  • Protein expression (Notch-1, Hes-1, caspase-3, NF-kappaB) analyzed by Western blotting.
  • NF-kappaB and caspase-3 activation evaluated by EMSA and colorimetric assays, respectively.

Main Results:

  • TNFalpha induced apoptosis in BGC-823 cells.
  • Over-activated Notch-1 (via ICN overexpression) reduced TNFalpha-induced growth suppression and apoptosis.
  • Down-regulation of Notch-1 by siRNA enhanced TNFalpha-induced apoptosis.
  • Over-activated Notch-1 partially suppressed TNFalpha-induced caspase-3 activation.
  • TNFalpha-induced NF-kappaB activation remained unaffected by Notch-1 over-activation.

Conclusions:

  • Over-activated Notch-1 significantly protects BGC-823 cells from TNFalpha-induced apoptosis.
  • This protective effect is mediated by decreased caspase-3 activation.
  • The mechanism is independent of NF-kappaB signaling.

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