COX‐2 is induced by the COX‐2 selective inhibitors celecoxib and etodolac and the non‐selective inhibitor ibuprofen in several human tumor cell lines (397.8)

The COX‐2 selective inhibitor, celecoxib, causes cancer cell death in vitro . However, the mechanism(s) behind the observed cytotoxic effects are still being debated. We have demonstrated that celecoxib treatment induces caspase‐dependent apoptosis in several human tumor cell lines (A375 melanoma, HT‐29 colon carcinoma and CRL‐1620 glioblastoma). Given protective effects of certain prostaglandins, we hypothesized that the apoptotic effects of celecoxib may be in part due to COX‐2 inhibition. However, western blotting for COX‐2 in A375, HT‐29 and CRL‐1620 cells treated with celecoxib for 24 hours revealed a surprising result. Celecoxib induced COX‐2 levels in each of these lines in a dose‐dependent manner. To determine whether COX‐2 induction by celecoxib is a class effect, we included the COX‐2 selective inhibitor etodolac and the non‐selective COX inhibitor ibuprofen. Etodolac treatment for 24 hours induced COX‐2 in a dose‐dependent manner in A375 and CRL‐1620 cells and at the highest dose in HT‐29 cells. Treatment with ibuprofen for 24 hours induced COX‐2 in a dose‐dependent manner in only A375 melanoma cells. These results demonstrate that the COX‐2 inhibitors celecoxib and etodolac induce protein expression of COX‐2 in several human tumor cell lines, whereas induction by ibuprofen was only seen in A375 tumor cells. These data demonstrate that specific and non‐COX specific NSAIDs induce COX‐2 expression.