title: Melatonin and celecoxib improve the outcomes in hamsters with experimental pancreatic cancer.
abstract: Pancreatic cancer is a major health problem because of the aggressiveness of the disease and the lack of effective systemic therapies. Melatonin (MEL) has antioxidant activity and prevents experimental genotoxicity. The specific inhibitor of cyclooxygenase-2 (COX-2), celecoxib (CEL), increases the efficacy of chemoradiotherapy in advanced pancreatic cancer. The objective of the study was the comparison and synergic effect of MEL and CEL during either the induction or progression phases of the tumor process, measuring parameters of oxidative stress, number of tumor nodules and survival of animals with pancreatic cancer. Pancreatic cancer was induced by N-nitrosobis (2-oxopropyl)amine) (BOP) in Syrian hamsters. Melatonin and/or CEL were administered during the induction, postinduction as well as during both phases. The presence of tumor nodules were observed macroscopically in pancreatic and splenic areas, and the levels of lipoperoxides (LPO), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) in pancreatic tissue were measured. The increases in tumor nodules and LPO as well as the reductions in GSH and enzymatic antioxidants in the pancreas induced by BOP were related to a lower survival rate of animals. The administration of MEL exerted a more potent beneficial effect than CEL treatment on the reduction in tumor nodules, oxidative stress and death of experimental BOP-treated animals. The combined treatment only exerted a synergistic beneficial effect when administered during the induction phase. Melatonin by itself had significant beneficial actions in improving the survival of hamsters.
authors.affiliation: Department of General Surgery, Virgen del Rocio University Hospital (IBiS), Seville, Spain. javierpadilloruiz@gmail.com
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Padillo
authors.forename: Juan F
authors.initials: JF
authors.lastname: Ruiz-Rabelo
authors.forename: Adolfo
authors.initials: A
authors.lastname: Cruz
authors.forename: María D
authors.initials: MD
authors.lastname: Perea
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Tasset
authors.forename: Pedro
authors.initials: P
authors.lastname: Montilla
authors.forename: Isaac
authors.initials: I
authors.lastname: Túnez
authors.forename: Jordi
authors.initials: J
authors.lastname: Muntané
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D002374:Catalase / Q000378:metabolism; D000068579:Celecoxib; D006224:Cricetinae; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology / Q000627:therapeutic use*; D008647:Mesocricetus; D018384:Oxidative Stress / Q000187:drug effects; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D052246:Cyclooxygenase 2 Inhibitors; D008054:Lipid Peroxides; D011720:Pyrazoles; D013449:Sulfonamides; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione; D000068579:Celecoxib; D008550:Melatonin