Blockade of cholecystokinin-2 receptor and cyclooxygenase-2 synergistically induces cell apoptosis, and inhibits the proliferation of human gastric cancer cells in vitro

Cancer Lett. 2008 May 18;263(2):302-11. doi: 10.1016/j.canlet.2008.01.012. Epub 2008 Feb 6.


Gastrin and cyclooxygenase-2 (COX-2) play important roles in the carcinogenesis and progression of gastric cancer. However, it remains unknown whether the combination of cholecystokinin-2 (CCK-2) receptor antagonist plus COX-2 inhibitor exerts synergistic anti-tumor effects on human gastric cancer. Here, we demonstrated that the combination of AG-041R (a CCK-2 receptor antagonist) plus NS-398 (a selective COX-2 inhibitor) treatment had synergistic effects on proliferation inhibition, apoptosis induction, down-regulation of Bcl-2 and up-regulation of Bax expression in MKN-45 cells. These results indicate that simultaneous targeting of CCK-2 receptor and COX-2 may inhibit gastric cancer development more effectively than targeting either molecule alone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cyclooxygenase 2 Inhibitors / pharmacology*
  • Gastrins / analysis
  • Humans
  • Receptor, Cholecystokinin B / antagonists & inhibitors*
  • Stomach Neoplasms / pathology*


  • Cyclooxygenase 2 Inhibitors
  • Gastrins
  • Receptor, Cholecystokinin B