[Suppressive effects of gamma-secretase inhibitor DAPT on the proliferation of pancreatic cancer cells]

Sichuan Da Xue Xue Bao Yi Xue Ban. 2013 Sep;44(5):699-702.
[Article in Chinese]

Abstract

Objective: To explore the effect of DAPT, a gamma-secretase inhibitor on the proliferation of pancreatic cancer cells and its underlying mechanism.

Methods: Three human pancreatic cancer cell lines as AsPC-1, BxPC-3 and MIAPaCa-2 were employed for in vitro experiments. Cell proliferation was tested by CCK-8 and cell apoptosis was examined by Annexin V/PI staining after the treatment of various concentrations of DAPT at different time.

Results: DAPT of 100 micromol/L significantly inhibited the proliferation of these 3 cell lines from day 3 to 5. DAPT of 50 micromol/L inhibited the proliferation of BxPC-3 and MIAPaCa-2 cells from day 3 to 5, whereas the effect of inhibition was only observed at day 5 in AsPC-I cell. DAPT of 10 micromol/L inhibited the proliferation of BxPC-3 and MIAPaCa-2 cells at day 5, whereas no effect was found in AsPC-1. Flow cytometry test showed that cell apoptosis rate was higher in DAPT treatment groups compared with control group.

Conclusion: DAPT could suppress the proliferation of pancreatic cancer cell, with the mechanism of promoting cell apoptosis.

Publication types

  • English Abstract
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid Precursor Protein Secretases / antagonists & inhibitors*
  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dipeptides / pharmacology*
  • Humans
  • Pancreatic Neoplasms / pathology*
  • Receptors, Notch / antagonists & inhibitors
  • Receptors, Notch / metabolism*
  • Signal Transduction

Substances

  • Dipeptides
  • N-(N-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester
  • Receptors, Notch
  • Amyloid Precursor Protein Secretases