INDOMETHACIN INTERFERES WITH EGF-INDUCED ACTIVATION OF ORNITHINE DECARBOXYLASE IN GASTRIC-CANCER CELLS

Background/Aims: Epidermal growth factor (EGF) has a wide variety of b iological activities in the protection of gastric mucosa against acute injury and the healing of gastric ulcer. However, the molecular basis of the EGF action remains unknown. EGF-induced activation of ornithin e decarboxylase (ODC) was examined, because ODC is a key enzyme for th e cell proliferation. Methods: The effects of epidermal growth factor (EGF) and indomethacin on ornithine decarboxylase (ODC) mRNA and enzym e activity were examined in gastric cancer derived KATO-III cells. Res ults: EGF induced both ODC mRNA expression and enzyme activation in a biphasic manner with the peaks at 0.5 and 3 h for mRNA and at 5 and 9 h for enzyme activity, respectively. Indomethacin pretreatment signifi cantly reduced EGF-induced ODC activation and was completely abolished for the first 5 h. Conclusion: Since it has been reported that both E GF and ODC are involved in cell migration and proliferation, two actio ns of EGF for gastric mucosal healing may be through, at least in part , this biphasic activation of ODC. Indomethacin suppresses and changes the response of ODC induced by EGF.