Functional analysis of Noxo1/Nox1 complex in gastritis and inflammation-associated gastric tumor development

• Project/Area Number: 15K18405
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: Kanazawa University
• Principal Investigator: Echizen Kanae 金沢大学, がん進展制御研究所, 博士研究員 (20743834)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 胃炎 / 胃がん / Nox1 / 慢性炎症 / Nox1複合体 / ROS / Noxo1

Outline of Final Research Achievements

H.pyroli infection-associated gastritis is one of the main causes of stomach cancer. However, molecular mechanism of gastritis formation is still unrevealed.In previous studies, our group reported that bone marrow-derived cells (BMDCs)-derived TNF-α promotes gastric tumor development. In this study, we investigated the molecular and genetic functions of Noxo1, which is a target of TNF-α, in gastritis and its associated tumorigenesis by using gastric cancer cells, gastritis model mice (C2mE mice) and sporadic gastric tumor model mice (Gan mice). Administration of a Nox inhibitor suppressed proliferation of gastric cancer cells in vitro and further inhibited metaplasia/hyperplasia formation in C2mE mice. We also found that this inhibitor also suppressed proliferation of stem-like cells in the neck region of stomach glands. Accordingly, Noxo1 and the Nox1 complex are possible effective preventive or therapeutic targets for gastritis and gastric cancer.

Research Products

• [Journal Article] Inflammation in gastric cancer: Interplay of the COX-2/prostaglandin E2 and Toll-like receptor/MyD88 pathways (2016)
  • Author(s): Kanae Echizen, Osamu Hirose, Yusuke Maeda and Masanobu Oshima
  • Journal Title: Cnacer Science Volume: 107 Issue: 4 Pages: 391-397
  • DOI: 10.1111/cas.12901
  • NAID: 120005819606
  • Peer Reviewed / Open Access
• [Journal Article] Myeloid Differentiation Factor 88 Signaling in Bone Marrow-Derived Cells Promotes Gastric Tumorigenesis by Generation of Inflammatory Microenvironment. (2016)
  • Author(s): Maeda Y, Echizen K, Oshima H, Yu L, Sakulsak N, Hirose O, Yamada Y, Taniguchi T, Jenkins BJ, Saya H, Oshima M.
  • Journal Title: Cancer prevention research Volume: 9 Issue: 3 Pages: 253-263
  • DOI: 10.1158/1940-6207.capr-15-0315
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Functional and genetic analysis of Noxo1/ROS in inflammation-associated gastric tumor development (2016)
  • Author(s): 越前佳奈恵、大島浩子、大島正伸
  • Organizer: 第75回 日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-10-06
• [Presentation] 炎症依存的な胃がん発生におけるNox1複合体/ROSの機能解析 (2016)
  • Author(s): 越前佳奈恵、大島浩子、大島正伸
  • Organizer: 第69回 日本酸化ストレス学会学術総会
  • Place of Presentation: 仙台国際センター会議棟
  • Year and Date: 2016-08-30
  • Invited
• [Presentation] 炎症依存的な胃がん発生におけるNoxo1の機能解析 (2015)
  • Author(s): 越前 佳奈恵
  • Organizer: 第74回 日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（名古屋市）
  • Year and Date: 2015-10-08
• [Book] 医学のあゆみ (2016)
  • Author(s): 越前佳奈恵、大島正伸 他
  • Total Pages: 126
  • Publisher: 医歯薬出版株式会社
• [Book] 実験医学 (2016)
  • Author(s): 大島浩子、越前佳奈恵、大島正伸 他
  • Total Pages: 138
  • Publisher: 羊土社