title: [Effect of polyunsaturated fatty acids ω-3 and ω-6 on angiogenesis formation in human gastric cancer].
abstract: OBJECTIVE
  To investigate the effects of polyunsaturated fatty acids (PUFA) ω-3 and ω-6, and their middle metabolites PGE2 and PGE3 on angiogenesis formation of gastric cancer, and to explore associated mechanism.
  
  
  METHODS
  The effects of ω-3, ω-6, PGE2, PGE3 on the proliferation and migration of human umbilical vein endothelial cell (HUVEC) were measured by proliferation and migration assay respectively. The angiogenesis assay in vivo was used to measure the effects of ω-3, ω-6, PGE2 and PGE3 on neovascularization. In all the assays, groups without ω-3, ω-6, PGE2 and PGE3 were designed as the control.
  
  
  RESULTS
  With the increased concentration of ω-6 from 1 μmol/L to 10 μmol/L, the proliferation ability of HUVECs enhanced, and the number of migration cells also increased from 28.2±3.0 to 32.8±2.1, which was higher than control group (21.2±3.2) respectively (both P<0.05). With the increased concentration of ω-3 from 1 μmol/L to 10 μmol/L, the proliferation ability of HUVECs was inhibited, and the number of migration cells decreased from 15.8±2.0 to 11.0±2.1, which was lower than control group (22.1±3.0) respectively (both P<0.05). In the angiogenesis assay, compared with control group (standard number: 43 721±4 654), the angiogenesis ability of HUVECs was significantly enhanced by ω-6 in concentration-dependent manner (1 μmol/L group: 63 238±4 795, 10 μmol/L group: 78 166±6 123, all P<0.01). Meanwhile, with the increased concentration of ω-3 from 1 μmol/L to 10 μmol/L, the angiogenesis ability was significantly decreased from 30 129±3 102 to 20 012±1 541(all P<0.01). The proliferation and migration ability of HUVECs were significantly promoted by ω-6 metabolites PGE2 (P<0.05) in a concentration-dependent manner. In contrast, ω-3 metabolites PGE3 significantly inhibited the proliferation and migration ability of HUVECs in a concentration-dependent manner (all P<0.05). After rofecoxib (a COX-2 specific inhibitor) inhibited the expression of COX-2, the expression level of PGE2 was significantly decreased in a dose-dependent manner. In co-culture system, whose gastric cancer cells expressed positive COX-2, ω-6 could increase angiogenesis of gastric cancer cells(P<0.01), but ω-3 could inhibit such angiogenesis(P<0.01). In co-culture system, whose gastric cancer cells did not express COX-2, ω-3 could inhibit the angiogenesis of gastric cancer cells (P<0.05), but ω-6 had no effect on angiogenesis.
  
  
  CONCLUSIONS
  The PUFA ω-6 can enhance the angiogenesis via the promotion of proliferation and migration of HUVECs, and COX-2 and PGE2 may play an important role in this process, whereas, the ω-3 can inhibit the angiogenesis through its middle metabolites PGE3 to inhibit the proliferation and migration of HUVECs. Results of this experiment may provide a new approach to inhibit and prevent the spread of gastric cancer.
authors.affiliation: Department of General Surgery, Gan Su provincial hospital, LanZhou 730000, China. tsmjc2013@163.com.
authors.forename: Jiachi
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of General Surgery, Gan Su provincial hospital, LanZhou 730000, China.
authors.forename: Yuntao
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of General Surgery, Gan Su provincial hospital, LanZhou 730000, China.
authors.forename: Tiankang
authors.initials: T
authors.lastname: Guo
authors.affiliation: Department of General Surgery, Gan Su provincial hospital, LanZhou 730000, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of General Surgery, Gan Su provincial hospital, LanZhou 730000, China.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of General Surgery, Gan Su provincial hospital, LanZhou 730000, China.
authors.forename: He
authors.initials: H
authors.lastname: Su
authors.affiliation: Ning Xia Medical University Graduate School, YinChuan 750004, China.
authors.forename: Xiaochang
authors.initials: X
authors.lastname: Chen
authors.affiliation: Ning Xia Medical University Graduate School, YinChuan 750004, China.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Ning Xia Medical University Graduate School, YinChuan 750004, China.
authors.forename: Qinjin
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Ning Xia Medical University Graduate School, YinChuan 750004, China.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Qi
mesh_terms: D000527:Alprostadil / Q000031:analogs & derivatives* / Q000494:pharmacology; D043925:Angiogenesis Inducing Agents / Q000378:metabolism / Q000494:pharmacology*; D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D002452:Cell Count / Q000379:methods; D045744:Cell Line, Tumor / Q000187:drug effects* / Q000502:physiology; D054443:Cell Migration Assays; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D018920:Coculture Techniques; D051546:Cyclooxygenase 2 / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology*; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D043371:Fatty Acids, Omega-6 / Q000378:metabolism / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007783:Lactones / Q000494:pharmacology; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D013274:Stomach Neoplasms / Q000503:physiopathology; D013450:Sulfones / Q000494:pharmacology
chemical_list: D043925:Angiogenesis Inducing Agents; D020533:Angiogenesis Inhibitors; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated; D007783:Lactones; D013450:Sulfones; C116926:rofecoxib; C033246:prostaglandin E3; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D000527:Alprostadil; D015232:Dinoprostone