Effects of Celebrex and Zyflo on liver metastasis and lipidperoxidation in pancreatic cancer in Syrian hamsters.
Selective inhibition of eicosanoid synthesis is thought to have effects on carcinogenesis in lung and colon cancer. However, it is still unknown whether pancreatic cancer might also be influenced. Therefore we evaluated the impact of selective cyclooxygenase-2 inhibitor Celebrex and selective 5-lipoxygenase inhibitor Zyflo on liver metastasis in a solid model of pancreatic adenocarcinoma in Syrian hamster. In week 33, the animals were sacrificed and incidence of pancreatic carcinomas and number and size of liver metastases were determined. Activities of antioxidative enzymes (GSHPX/SOD) and concentrations of products of lipidperoxidation were measured in liver metastases and non-metastatic hepatic tissue. The incidence (54.5 vs. 100%), number (3.17 +/- 0.98 vs. 6.75 +/- 0.71) and size (2.67 +/- 1.97 vs. 11.75 +/- 1.98 mm2) of liver metastases were decreased by combined therapy of Zyflo and Celebrex (P < 0.05). Furthermore, activities of GSHPX ([73.77 +/- 5.67]*10(5) vs. [15.49 +/- 4.02]*10(5) U/mg prot.; P < 0.05) and SOD (474.92 +/- 108.8 vs. 127.89 +/- 38.75 U/mg prot.; P < 0.05) were increased, while lipidperoxidation (0.31 +/- 0.08 nmol/mg prot. vs. 1.54 +/- 0.55 nmol/mg prot.; P < 0.05) was decreased by combination therapy, in non-metastatic hepatic tissue. Moreover, combined therapy increased lipidperoxidation in liver metastases (0.47 +/- 0.09 vs. 1.95 +/- 0.12 nmol/mg prot.; P < 0.05). Thus, a combination of Celebrex and Zyflo might be a new concept to decrease tumour growth in liver metastases in advanced pancreatic cancer.
Wenger
F A
FA
Clinic of General, Visceral, Vascular and Thoracic Surgery, Charité Campus Mitte, Humboldt-University of Berlin, Germany. charipanc@aol.com
Kilian
M
M
Bisevac
M
M
Khodadayan
C
C
von Seebach
M
M
Schimke
I
I
Guski
H
H
Müller
J M
JM
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000068579:Celecoxib; D006224:Cricetinae; D006918:Hydroxyurea / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D015227:Lipid Peroxidation / Q000187:drug effects*; D016859:Lipoxygenase Inhibitors / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000556:secondary*; D008297:Male; D008647:Mesocricetus; D009362:Neoplasm Metastasis / Q000517:prevention & control; D010190:Pancreatic Neoplasms / Q000473:pathology*; D011720:Pyrazoles; D013449:Sulfonamides / Q000627:therapeutic use*; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016859:Lipoxygenase Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D017392:Thiobarbituric Acid Reactive Substances; D013482:Superoxide Dismutase; D000068579:Celecoxib; C063449:zileuton; D006918:Hydroxyurea