Proton pump inhibitors (PPIs) are effective at preventing non-steroidal anti-inflammatory drug (
NSAID)-induced
gastric ulcers. They are also superior to
histamine H(2)-receptor antagonists and
misoprostol in treating
NSAID-induced
gastric ulcer healing. This study explored whether
omeprazole, a PPI, can modulate
ulcer healing through epithelial cell proliferation and/or cell migration using a rat normal gastric epithelial cell line (RGM-1). Flow cytometry was used to determine cell proliferation and an artificial
wound model was used to measure cell migration. Western blot analysis was performed to evaluate the possible mechanisms of action.
Omeprazole treatment (10(-8), 10(-6) and 10(-4)M) for 12 and 24 h did not promote cell proliferation. However, similar doses of the drug (10(-6) and 10(-4)M) incubated for 24-48 h significantly promoted the basal cell migration of gastric epithelial cells. Further, the higher concentration of
omeprazole (10(-4)M) reversed the inhibitory action of
indometacin (10(-5)) on cell migration. Western blot results showed that
omeprazole did not increase
cyclooxygenase-2 expression and did not activate signal transduction pathways, including
extracellular signal-regulated kinase (ERK1/ERK2), P38 mitogenic-activated
protein kinase, and
phosphatidyl inositol 3-kinase. The results suggest that
omeprazole is beneficial in basal
ulcer healing and it reversed the adverse action of
indometacin on
ulcer repair under
acid-independent conditions. These actions are likely to be mediated through the promotion of gastric epithelial cell migration but not cell proliferation.