Journal
ONCOLOGY LETTERS
Volume 13, Issue 1, Pages 243-249Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/ol.2016.5382
Keywords
DHA; MMP-9; PPAR-gamma; invasion; NF-kappa B; MCF-7
Categories
Funding
- Korea Atomic Energy Research Institute [NRF-2015M2A2A6021673]
- National Research Foundation of Korea - Korean government [2011-0030130]
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Docosahexaenoic acid (DHA) is an omega-3 fatty acid that is considered to have applications in cancer prevention and treatment. The beneficial effects of DHA against cancer metastasis are well established; however, the mechanisms underlying these effects in breast cancer are not clear. Cell invasion is critical for neoplastic metastasis, and involves the degradation of the extracellular matrix by matrix metalloproteinase (MMP)-9. The present study investigated the inhibitory effect of DHA on MMP-9 expression and cell invasion induced by 12- O-tetradecanoylphorbol-13-acetate (TPA) in the MCF-7 breast cancer cell line. DHA inhibited the TPA-induced activation of mitogen-activated protein kinase (MAPK) and the transcription of nuclear factor (NF)-kappa B, but did not inhibit the transcription of activator protein-1. DHA increased the activity of peroxisome proliferator-activated receptor (PPAR)-gamma, an effect that was reversed by the application of the PPAR-gamma antagonist GW9662. In addition, combined treatment with GW9662 and DHA increased NF-kappa B-related protein expression. These results indicate that DHA regulates MMP-9 expression and cell invasion via modulation of the MAPK signaling pathway and PPAR-gamma/NF-kappa B activity. This suggests that DHA could be a potential therapeutic agent for the prevention of breast cancer metastasis.
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