Denkins Y, Kempf D, et al. Role of omega-3 polyunsaturated
fatty acids on cyclooxygenase-2 metabolism in brain-metastatic
melanoma. J. Lipid Research, 2005; 46: 1278-1284.
Cyclooxygenase-2 (COX-2) is important in the progression of epithelial
tumors. Evidence indicates that omega-6 PUFAs such as arachidonic
acid (AA) promote the growth of tumor cells; however, omega-3
fatty acids [eicosapentaenoic acid (EPA) and docosahexaenoic
acid (DHA)] inhibit tumor cell proliferation.
We investigated the effects of omega-3 PUFA on the expression
and function of COX-2 in 70W, a human melanoma cell line that
metastasizes to the brain in nude mice.
We show that 1) tumor necrosis factor-alpha upregulates the expression
of both COX-2 mRNA and prostaglandin E2 (PGE2) production, and 2)
omega-3 and omega-6 PUFA regulate COX-2 mRNA expression and PGE2
production. AA increased COX-2 mRNA expression and prostaglandin
production in omega-6-stimulated 70W cells.
Conversely, COX-2 mRNA expression decreased in cells incubated
with EPA or DHA. AA increased MatrigelTM invasion 2.4-fold, whereas
EPA or DHA did not.
Additionally, PGE2 increased in vitro invasion 2.5-fold, whereas
exposure to PGE3 significantly decreased invasion.
Our results demonstrate that incubation of 70W cells with either
AA or PGE2 increased invasiveness, whereas incubation with EPA
or DHA downregulated both COX-2 mRNA and protein expression,
with a subsequent decrease in MatrigelTM invasion.
Taken together, these results indicate that omega-3 PUFA regulate
COX-2-mediated invasion in brain-metastatic melanoma.
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