Inhibition of cyclooxygenase-2 decreases breast cancer cell motility, invasion and matrix metalloproteinase expression

Breast cancer cells (Hs578T, MDA-MB-231 and MCF-7) were treated with selective COX-2 inhibitors (NS-398 and Niflumic acid, NA). Cell proliferation was measured by staining with erythrosin B and counting the viable cells using a hemacytometer. Cell migration and invasion were measured using migration and invasion chamber systems. MMP expression was determined by enzyme immunoassay (secreted protein) and real-time quantitative polymerase chain reaction (mRNA).Our results show that there is a decline in proliferation, migration and invasion by the Hs578T and MDA-MB-231 breast cancer cell lines in the presence of either low concentrations (1 μM or lower) NA or NS-398. We also report that MMP mRNA and protein expression by Hs578T cells is inhibited by NS-398; there was a 50% decrease by 100 μM NS-398. PGE2 completely reversed the inhibitory effect of NS-398 on MMP mRNA expression.Our data suggests that COX-2-dependent activity is a necessary component for cellular and molecular mechanisms of breast cancer cell motility and invasion. COX-2 activity also modulates the expression of MMPs, which may be a part of the molecular mechanism by which COX-2 promotes cell invasion and migration. The studies suggest that COX-2 assists in determining and defining the metastatic signaling pathways that promote the breast cancer progression to metastasis.Numerous studies indicate that cyclooxygenase-2 (COX-2) is highly expressed in a variety of human cancers, including colorectal, breast and prostate. In breast cancer, the expression of the COX-2 gene is associated with high tumor grade [1], which suggests it may serve as a prognostic biomarker for the presence of breast cancer. Researchers also found high expression of COX-2 in highly invasive estrogen independent breast cancer cell lines, (MDA-MB-231 (MDA-231) and Hs578T) as well as 12, 0-tetradecanoylphorbol-13-acetate (TPA)-induced COX-2 expression, while a poorly invasive and estrogen dependent cell line (MCF-7) did not express COX