Oncotarget

Research Papers:

Suppressed Helicobacter pylori-associated gastric tumorigenesis in Fat-1 transgenic mice producing endogenous ω-3 polyunsaturated fatty acids

Young-Min Han, Kyung-Jo Kim, Migyeung Jeong, Jong-Min Park, Eun-Jin Go, Jing X Kang, Sung Pyo Hong and Ki Baik Hahm _

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Oncotarget. 2016; 7:66606-66622. https://doi.org/10.18632/oncotarget.11261

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Abstract

Young-Min Han1,*, Kyung-Jo Kim2,*, Migyeung Jeong1, Jong-Min Park1, Eun-Jin Go1, Jing X Kang3, Sung Pyo Hong4, Ki Baik Hahm1,4

1CHA Cancer Prevention Research Center, CHA Cancer Institute, CHA University, Seoul, Korea

2Department of Gastroenterology, University of Ulsan, Seoul Asan Medical Center, Seoul, Korea

3Laboratory for Lipid Medicine and Technology, Massachusetts General Hospital, Harvard Medical School, Boston, USA

4Department of Gastroenterology, CHA Bundang Medical Center, Seongnam, Korea

*These authors have contributed equally to this work

Correspondence to:

Ki Baik Hahm, email: hahmkb@cha.ac.kr

Keywords: Fat-1 transgenic mice, COX-2, 15-PGDH, ω-3 PUFAs, anti-proliferation

Received: April 27, 2016     Accepted: July 28, 2016     Published: August 12, 2016

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.


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