title: Suppressed Helicobacter pylori-associated gastric tumorigenesis in Fat-1 transgenic mice producing endogenous ω-3 polyunsaturated fatty acids.
abstract: Dietary approaches to preventing Helicobacter pylori (H. pylori)-associated gastric carcinogenesis are widely accepted because surrounding break-up mechanisms are mandatory for cancer prevention, however, eradication alone has been proven to be insufficient. Among these dietary interventions, omega-3-polyunsaturated-fatty acids (ω-3 PUFAs) are often the first candidate selected. However, there was no trial of fatty acids in preventing H. pylori-associated carcinogenesis and inconclusive results have been reported, likely based on inconsistent dietary administration. In this study, we developed an H. pylori initiated-, high salt diet promoted-gastric tumorigenesis model and conducted a comparison between wild-type (WT) and Fat-1-transgenic (TG)-mice. Gross and pathological lesions in mouse stomachs were evaluated at 16, 24, 32, and 45 weeks after H. pylori infection, and the underlying molecular changes to explain the cancer preventive effects were investigated. Significant changes in: i) ameliorated gastric inflammations at 16 weeks of H. pylori infection, ii) decreased angiogenic growth factors at 24 weeks, iii) attenuated atrophic gastritis and tumorigenesis at 32 weeks, and iv) decreased gastric cancer at 45 weeks were all noted in Fat-1-TG-mice compared to WT-mice. While an increase in the expression of Cyclooxygenase (COX)-2, and reduced expression of the tumor suppressive 15-PGDH were observed in WT-mice throughout the experimental periods, the expression of Hydroxyprostaglandin dehydrogenase (15-PGDH) was preserved in Fat-1-TG-mice. Using a comparative protein array, attenuated expressions of proteins implicated in proliferation and inflammation were observed in Fat-1-TG-mice compared to WT-mice. Conclusively, long-term administration of ω-3 PUFAs can suppress H. pylori-induced gastric tumorigenesis through a dampening of inflammation and reduced proliferation in accordance with afforded rejuvenation.
authors.affiliation: CHA Cancer Prevention Research Center, CHA Cancer Institute, CHA University, Seoul, Korea.
authors.forename: Young-Min
authors.initials: YM
authors.lastname: Han
authors.affiliation: Department of Gastroenterology, University of Ulsan, Seoul Asan Medical Center, Seoul, Korea.
authors.forename: Kyung-Jo
authors.initials: KJ
authors.lastname: Kim
authors.affiliation: CHA Cancer Prevention Research Center, CHA Cancer Institute, CHA University, Seoul, Korea.
authors.forename: Migyeung
authors.initials: M
authors.lastname: Jeong
authors.affiliation: CHA Cancer Prevention Research Center, CHA Cancer Institute, CHA University, Seoul, Korea.
authors.forename: Jong-Min
authors.initials: JM
authors.lastname: Park
authors.affiliation: CHA Cancer Prevention Research Center, CHA Cancer Institute, CHA University, Seoul, Korea.
authors.forename: Eun-Jin
authors.initials: EJ
authors.lastname: Go
authors.affiliation: Laboratory for Lipid Medicine and Technology, Massachusetts General Hospital, Harvard Medical School, Boston, USA.
authors.forename: Jing X
authors.initials: JX
authors.lastname: Kang
authors.affiliation: Department of Gastroenterology, CHA Bundang Medical Center, Seongnam, Korea.
authors.forename: Sung Pyo
authors.initials: SP
authors.lastname: Hong
authors.affiliation: CHA Cancer Prevention Research Center, CHA Cancer Institute, CHA University, Seoul, Korea.|Department of Gastroenterology, CHA Bundang Medical Center, Seongnam, Korea.
authors.forename: Ki Baik
authors.initials: KB
authors.lastname: Hahm
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D063646:Carcinogenesis / Q000378:metabolism*; D015525:Fatty Acids, Omega-3 / Q000096:biosynthesis*; D016481:Helicobacter Infections / Q000150:complications; D016480:Helicobacter pylori; D007249:Inflammation / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008822:Mice, Transgenic; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology
chemical_list: D015820:Cadherins; D015525:Fatty Acids, Omega-3; C502406:fat1 protein, mouse
keywords: 15-PGDH; COX-2; Fat-1 transgenic mice; anti-proliferation; ω-3 PUFAs