To elucidate the possible role of these pathways in IBU-mediated upregulation of COX-2 expression, we analyzed the levels of phosphorylated AKT and phosphorylated ERK1/2 in IBU-treated hypoxic cancer cell lines and confirmed that IBU activated both signaling pathways in a dose- and time- dependent manner (Fig 4B). Here, MAPK3 is linked to cancer.