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Anticancer Res. 2000 Jul-Aug;20(4):2625-31.

Blockade of cyclooxygenase-2 inhibits proliferation and induces apoptosis in human pancreatic cancer cells.

Author information

1
Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, NE 68178, USA.

Abstract

Cyclooxygenase (COX), also referred to as prostaglandin endoperoxide synthase, is a key enzyme in the conversion of arachidonic acid to prostaglandins and other eicosanoids. Epidemiologic, animal and in vitro observations show a positive correlation between the expression of COX (especially COX-2) and colonic cancer development, growth and apoptosis. Constitutive expression of COX-2 in human pancreatic cancer cells was recently reported. To evaluate the potential role of COX in pancreatic cancer, RT-PCR was used to determine the constitutive expression of COX-2 in four pancreatic cancer cell lines. MiaPaCa2, PANC-1, HPAF, ASPC-1. The effect of COX blockade with either the general COX inhibitor, indomethacin, or the specific COX-2 inhibitor, NS-398, on [3H]-thymidine incorporation and cell number was investigated in these four pancreatic cancer cell lines. In addition, the effects of these COX inhibitors on pancreatic cancer cell apoptosis was evaluated by DNA propidium iodide staining and the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay. All four human pancreatic cancer cell lines expressed COX-2 and their proliferation was concentration- and time-dependently inhibited by both indomethacin andNS398. Substantial apoptosis was also induced by treatment of pancreatic cancer cells with either indomethacin or NS398, as indicated by both DNA propidium iodide staining and the TUNEL assay. Furthermore, indomethacin and NS398 were equipotent for growth inhibition and induction of apoptosis, indicating that eicosanoid synthesis via COX-2 is involved in pancreatic cancer cell proliferation and survival. In conclusion, these findings suggest that the COX pathway, especially COX-2, contributes to the growth and apoptosis of pancreatic cancer. Specific COX-2 inhibitors are likely to be valuable for the treatment and prevention of this deadly cancer.

PMID:
10953335
[Indexed for MEDLINE]

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