Scope: Pancreatic cancer remains a disease of poor prognosis, with alternate strategies being sought to improve therapeutic efficacy. Omega-3 fatty acids have shown clinical benefit, and mechanisms of action are under investigation.
Methods And Results: Proliferation assays, flow cytometry, invasion assays, ELISA and western blotting were used to investigate efficacy of omega-3 fatty acids alone and in combination with gemcitabine. The docosahexanoic acid (DHA)/eicosapentanoic acid (EPA) combination, Lipidem™, in combination with gemcitabine inhibited growth in pancreatic cancer and pancreatic stellate cell (PSC) lines, with PSCs exhibiting greatest sensitivity to this combination. Invasion of pancreatic cancer cells and PSCs in a 3D spheroid model, was inhibited by combination of gemcitabine with Lipidem™. PSCs were required for cancer cell invasion in an organotypic co-culture model, with invasive capacity reduced by Lipidem™ alone. Platelet-derived growth factor (PDGF) is a key cytokine in pro-proliferative and invasion signalling, and thus a critical regulator of interactions between pancreatic cancer cells and adjacent stroma. Platelet-derived growth factor (PDGF-BB) secretion was completely inhibited by the combination of Lipidem™ with gemcitabine in cancer cells and PSCs.
Conclusion: Lipidem™ in combination with gemcitabine, has anti-proliferative and anti-invasive efficacy in vitro, with pancreatic stellate cells exhibiting the greatest sensitivity to this combination.
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| http://dx.doi.org/10.1002/mnfr.201500755 | DOI Listing |
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