Effects of Celebrex and Zyflo on BOP-induced pancreatic cancer in Syrian hamsters.
OBJECTIVE
Selective inhibition of eicosanoid synthesis decreases inflammation, however, it is still unknown whether oxidative stress and carcinogenesis might be influenced in ductal pancreatic ductal cancer as well.


METHODS
120 male hamsters were randomized into 8 groups (n = 15). While control group 1-4 received 0.5 ml normal saline s.c. weekly for 16 weeks, groups 5-8 were injected 10 mg BOP/kg body weight to induce pancreatic cancer. After establishment of pancreatic cancer, groups 1 and 5 received no therapy, groups 2 and 6 were fed 7 mg Celebrex daily, groups 3 and 7 were given 28 mg Zyflo and groups 4 and 8 received Celebrex and Zyflo orally daily in weeks 17-32. In week 33, all animals were sacrificed, macroscopic size of pancreatic carcinomas was measured, incidence of pancreatic cancer was analyzed histopathologically and activities of antioxidative enzymes and concentration of products of lipid peroxidation in tumor-free and pancreatic intratumoral tissue were determined.


RESULTS
Incidence and size of macroscopic pancreatic carcinomas were decreased by single therapy with Zyflo as well as combined therapy (Zyflo + Celebrex). Activities of antioxidative enzymes were increased and the concentration of products of lipid peroxidation was decreased in tumor-free pancreas. On the other hand, lipid peroxidation was increased in pancreatic tumors.


CONCLUSIONS
Zyflo alone or in combination with Celebrex reduce tumor growth in pancreatic cancer and thus might be a new therapeutic option in advanced pancreatic cancer.
Wenger
F A
FA
Clinic of General, Visceral, Vascular and Thoracic Surgery, Charité Campus Mitte, Schumannstrasse 20/21, D-10117 Berlin, Germany. charipanc@aol.com
Kilian
M
M
Achucarro
P
P
Heinicken
D
D
Schimke
I
I
Guski
H
H
Jacobi
C A
CA
Müller
J M
JM
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000068579:Celecoxib; D006224:Cricetinae; D005978:Glutathione / Q000378:metabolism; D006918:Hydroxyurea / Q000031:analogs & derivatives* / Q000494:pharmacology*; D015994:Incidence; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D008297:Male; D008647:Mesocricetus; D010179:Pancreas / Q000201:enzymology / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011720:Pyrazoles; D013449:Sulfonamides / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000970:Antineoplastic Agents; D016859:Lipoxygenase Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D017392:Thiobarbituric Acid Reactive Substances; D013482:Superoxide Dismutase; D005978:Glutathione; D000068579:Celecoxib; C063449:zileuton; D006918:Hydroxyurea