The omega-3 polyinsaturated fatty acid eicosapentaenoic acid inhibits mouse MC-26 colorectal cancer cell liver metastasis via inhibition of prostaglandin E2-dependent cell motility
Menée sur un modèle murin, cette étude montre que l'acide icosapentaénoïque, un acide gras poly-insaturé de la famille des oméga 3, peut inhiber le développement de métastases hépatiques d'un cancer colorectal en bloquant la motilité des cellules tumorales du côlon
purpose: The omega (omega)-3 polyunsaturated fatty acid (PUFA) eicosapentaenoic acid (EPA) has anti-neoplastic activity at early stages of colorectal carcinogenesis, relevant to chemoprevention of colorectal cancer (CRC). We tested the hypothesis that EPA also has anti-CRC activity at later stages of colorectal carcinogenesis, relevant to treatment of metastatic CRC, via modulation of E-type prostaglandin (PG) synthesis. Methods: A BALB/c mouse model, in which intra-splenic injection of syngeneic MC-26 mouse CRC cells leads to development of liver metastases, was used. Dietary EPA was administered in the free fatty acid (FFA) form for 2 weeks before and after ultrasound-guided intra-splenic injection of 1 x 10(6) MC-26 cells (n = 16 each group). Results: Treatment with 5% (w/w) EPA-FFA was associated with a reduced MC-26 mouse CRC cell liver tumour burden compared with control animals (median liver weight 1.62g versus 1.03g; P < 0.034). Administration of 5% EPA-FFA was also linked to a significant increase in tumour EPA incorporation and lower intra-tumoral PGE(2) levels (with concomitant increased production of PGE(3) ). Liver tumours from 5% EPA-FFA treated mice demonstrated decreased bromodeoxyuridine-positive CRC cell proliferation and reduced phosphorylated extracellular signal-related kinase 1/2 expression at the invasive edge of tumours. A concentration-dependent reduction in MC-26 CRC cell Transwell(R) migration following EPA-FFA treatment (50-200microM) in vitro was rescued by exogenous PGE(2) (10microM) and PGE(1) -alcohol (1microM). Conclusions: EPA-FFA inhibits MC-26 CRC cell liver metastasis. EPA incorporation is associated with a 'PGE(2) to PGE(3) switch' in liver tumours. Inhibition of PGE(2) -EP4 receptor-dependent CRC cell motility likely contributes to the anti-neoplastic activity of EPA. (c) 2012 The Authors. British Journal of Pharmacology (c) 2012 The British Pharmacological Society.
http://onlinelibrary.wiley.com/doi/10.1111/j.1476-5381.2012.01882.x/abstract