The effect of cyclooxygenase inhibitor diclofenac on experimental murine colon carcinoma.
BACKGROUND
Cyclooxygenase-2 (Cox-2) has been found to be overexpressed in several types of human cancers and its role in tumorigenesis has been proposed. The aim of this study was to investigate the effects of the cyclooxygenase inhibitor diclofenac on the growth of murine C-26 colon carcinoma cells.


METHODS
Expression of Cox-2 mRNA and protein was examined by RT-PCR analysis and immunohistochemistry, respectively. By using MTT-assay, we examined the effects of diclofenac at various concentrations on the growth of C-26 cells in vitro. The effect of diclofenac on the growth of the C-26 tumor in syngeneic mice was also investigated.


RESULTS
By RT-PCR, Cox-2 mRNA was detected in C-26 cells. Cox-2 protein was localized to C-26 cells and treatment with diclofenac resulted in apoptotic cell death in a dose-dependent manner. Diclofenac administered in drinking water resulted in growth inhibition of C-26 tumor in mice and correlated with plasma levels of both PGE2 and TXB2.


CONCLUSIONS
Our data show that diclofenac may be a potential agent for the prevention and treatment of human colon cancer.
Falkowski
M
M
Department of Experimental Pathology, Medical Faculty, University of Tromsö, N-9037, Tromsö, Norway.
Skogstad
S
S
Shahzidi
S
S
Smedsröd
B
B
Sveinbjörnsson
B
B
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004008:Diclofenac / Q000494:pharmacology*; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D005260:Female; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D012333:RNA, Messenger; D004008:Diclofenac; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone