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Schematic diagram showing the formation of the PGE2-COX-2 positive feedback loop. PGE2 induces COX-2 expression through any functional EP receptor. The activation of PI3K-AKT and CREB by PGE2 is required for the upregulation of COX-2 expression. Elevated COX-2 expression is responsible for the PGE2-mediated pro-tumor effects. Targeting both PI3K-AKT and COX-2 effectively abrogates PGE2-mediated increase in cell proliferation and migration.
