Effects of Capecitabine and Celecoxib in Experimental Pancreatic Cancer

Introduction: Pancreatic cancer is a major health problem because of its aggressiveness and the lack of effective systemic therapies. The aim of the study was the identification of beneficial properties of combined celecoxib and capecitabine treatment during an experimental pancreatic cancer model. Methods: N-nitrosobis (2-oxopropyl) amine (BOP) was used as a tumoral agent for 12 weeks. Celecoxib and capecitabine were administered either as monotherapy or combined 12 weeks after cancer induction for a period of 24 weeks. The presence of well-developed or moderate adenocarcinoma was evaluated in the pancreas. Several markers of stress, such as lipoperoxides, reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GHS-Px) were determined. Results: BOP induced the presence of pancreatic tumors associated with a rise in lipoperoxides and the reduction of the antioxidant status in the pancreas. The administration of celecoxib and capecitabine reduced the number of animals with tumors (33 and 66%, respectively). This antitumoral effect was associated with a recovery of GSH, SOD and CAT activity in the pancreas of BOP-treated animals. The combined treatment exerted a synergic antitumoral effect and reduced pancreatic oxidative stress. Conclusion: The combined administration of celecoxib and capecitabine exerted a synergistic antitumoral effect and increased the antioxidant status restoration in pancreatic cancer. Copyright (C) 2010 S. Karger AG, Basel and IAP