Gastric mucosal cell model for estimating relative gastrointestinal toxicity of non-steroidal anti-inflammatory drugs

Prostaglandins Leukot Essent Fatty Acids. 2006 Jul;75(1):9-17. doi: 10.1016/j.plefa.2006.04.006. Epub 2006 Jun 27.


The study objective was to characterize the AGS human gastric mucosal cell line as a model for estimating gastrointestinal toxicity of COX-inhibiting compounds. Rofecoxib, celecoxib, nimesulide, ibuprofen, indomethacin, aspirin, salicylic acid, naproxen and acetaminophen were tested for inhibition of COX-2-mediated prostaglandin E2 synthesis in A549 and AGS cells. The IC50 ratio AGS/A549 was calculated as an estimate of the therapeutic index (TI) for gastrointestinal toxicity. Calculated IC50 values of non-steroidal anti-inflammatory drugs (NSAIDs) in A549 cells were in excellent agreement with published values (r = 0.996; P < 0.005). Calcium ionophore induction of arachidonic acid release in AGS cells provided TI similar to those using platelets and A549 cells (r = 0.918; P < 0.01). The AGS/A549 model exhibited lower TI than the platelet/A549 model. Spearman ranking correlated clinical NSAID gastropathy with lower AGS TI values. The AGS cell line has excellent potential to serve as a model for assessing the gastrointestinal effects of COX-inhibiting compounds.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / toxicity*
  • Blood Platelets / drug effects
  • Cell Line
  • Cell Survival / drug effects
  • Cyclooxygenase 2 Inhibitors / toxicity
  • Dinoprostone / biosynthesis
  • Gastric Mucosa / drug effects*
  • Gastric Mucosa / pathology
  • Gastrointestinal Diseases / chemically induced*
  • Humans
  • Inhibitory Concentration 50
  • Models, Biological


  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase 2 Inhibitors
  • Dinoprostone