Nimesulide inhibits proliferation and induces apoptosis of pancreatic cancer cells by enhancing expression of PTEN

: Pancreatic cancer is the fourth leading cause of cancer-associated cases of mortality worldwide. Prostaglandin-endoperoxide synthase 2 (COX-2) is considered a therapeutic target for prevention of pancreatic cancer. Nimesulide, a selective COX-2 inhibitor, can induce cell apoptosis, resulting in an anti-cancer effect. However, the mechanism underlying this effect remains to be elucidated. The present study aimed to evaluate the effects of nimesulide on proliferation of PANC-1 cells using an MTT assay. Apoptosis was evaluated by DNA laddering and Annexin V-fluorescein isothiocyanate/propidium iodide-stained flow cytometry. Furthermore, western blot analysis was used to elucidate the mechanism underlying nimesulide treatment in PANC-1 cells. It was determined that proliferation of PANC-1 cells was inhibited by nimesulide in a dose-dependent manner. Nimesulide promoted apoptosis of PANC-1 cells. Western blot analysis demonstrated that nimesulide increased expression of cleaved caspase-3 and apoptosis regulator Bax (Bcl-2 associated protein X), and decreased the expression of pro-caspase-3 and apoptosis regulator Bcl-2 (B-cell lymphoma 2). Furthermore, nimesulide enhanced expression of phosphatase and tensin homolog (PTEN), and decreased the expression level of COX-2 and vascular endothelial growth factor. In summary, the results of the present study demonstrated that nimesulide could induce apoptosis and inhibit growth of PANC-1 cells by enhancing the expression of PTEN, which indicates the potential of nimesulide to prevent tumor angiogenesis.