Co-Administration of Fish Oil With Signal Transduction Inhibitors Has Anti-Migration Effects in Breast Cancer Cell Lines, in vitro
Zoë Davison, Robert I. Nicholson, Stephen Hiscox, Charles M. Heard*
School of Pharmacy & Pharmaceutical Sciences, Cardiff University, CF10 3NB, Cardiff, United Kingdom
There is an urgent need for new therapies to treat cancer metastasis. Fish oil, with high omega 3 fatty acid content, has shown anticancer activity and signal transduction inhibitors have shown anti-metastatic properties.
To provide preliminary in vitro data on the anti-migration potential of signal transduction inhibitors and co-administered fish oil.
MCF-7, TamR and FasR breast cancer cell lines were used to determine the effects of combinations of PD98059, LY294002 and fish oil in growth assays. Modulations of p-Src and COX-2, both mediators of motility and invasion, were then determined by Western blotting and IHC to ascertain effects on migration potential.
Migration rates for the three cell lines examined were ranked: FasR>TamR>MCF-7 (p <0.05). Addition of fish oil reduced the number of TamR cells migrating after 48h (p <0.05), while the addition of PD98059 and LY294002 also decreased migratory potential of TamR cells (p <0.05). Addition of PD98059 and LY294002 to TamR cells did not result in a significant decrease in p-Src levels; as was the case when PD98059, LY294002 and 4-hydroxytamoxifen were added to MCF-7 cells. However, the co-administration of fish oil markedly reduced p-Src and COX-2 expression in both cell lines.
Co-administration of a commercial fish oil with signal transduction inhibitors results in decreased cell migration via an unknown co-operative mechanism and could constitute a novel approach for the treatment of breast cancer metastasis.
Keywords: Cancer, Cell migration, Signal transduction inhibitor, PD98059, LY294002, Fish oil.
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* Address correspondence to this author at the School of Pharmacy & Pharmaceutical Sciences, Cardiff University, CF10 3NB, Cardiff, United Kingdom; Tel: +442920875819; Fax +44 2920 875819, E-mail: firstname.lastname@example.org# All authors contributed equally to the work.