title: Targeting pancreatic cancer using a combination of gemcitabine with the omega-3 polyunsaturated fatty acid emulsion, Lipidem™.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Cancer Studies, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, , University of Leicester, Leicester, LE2 7LX, United Kingdom.|Department of Hepatobiliary Surgery, Leicester General Hospital, Gwendolen Road, Leicester, LE5 4PW, United Kingdom.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Haqq
authors.affiliation: Department of Cancer Studies, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, , University of Leicester, Leicester, LE2 7LX, United Kingdom.
authors.forename: Lynne M
authors.initials: LM
authors.lastname: Howells
authors.affiliation: Department of Hepatobiliary Surgery, Leicester General Hospital, Gwendolen Road, Leicester, LE5 4PW, United Kingdom.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Garcea
authors.affiliation: Department of Hepatobiliary Surgery, Leicester General Hospital, Gwendolen Road, Leicester, LE5 4PW, United Kingdom.
authors.forename: Ashley R
authors.initials: AR
authors.lastname: Dennison
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D000077214:Becaplermin; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018920:Coculture Techniques; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D006801:Humans; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D058954:Pancreatic Stellate Cells / Q000187:drug effects / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D000093542:Gemcitabine
chemical_list: D015525:Fatty Acids, Omega-3; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D003841:Deoxycytidine; D000077214:Becaplermin; D017479:Receptors, Platelet-Derived Growth Factor; D000093542:Gemcitabine
keywords: Fishoil; Pancreatic cancer; Pancreatic stellate cells; Platelet-derived growth factor; Polyunsaturated fatty acids