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2013 Fiscal Year Final Research Report

Preclinical study for Head and Neck Cancer using rAAV-GALR2

Research Project

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Project/Area Number 23592539
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Otorhinolaryngology
Research InstitutionJichi Medical University

Principal Investigator

KANAZAWA Takeharu  自治医科大学, 医学部, 准教授 (20336374)

Co-Investigator(Kenkyū-buntansha) ICHIMUR Keiichi  自治医科大学, 医学部, 教授 (00010471)
MIZUKAMI Hiroaki  自治医科大学, 医学部, 准教授 (20311938)
UEHARA Takayuki  琉球大学, 医学部, 助教 (00644402)
Project Period (FY) 2011 – 2013
Keywords遺伝子治療 / GALR2 / 癌抑制遺伝子 / 頭頸部癌 / AAV
Research Abstract

Galanin and its receptors, GALR1 and GALR2, are known tumor suppressors and potential therapeutic targets in head and neck squamous cell carcinoma (HNSCC). In this study, we first transduced HEp-2 and KB cell lines using a recombinant adeno-associated virus (rAAV)-green fluorescent protein (GFP) vector and confirmed a high GFP expression rate (>90%) in both cell lines. Next, we demonstrated that GALR2 expression in the presence of galanin suppressed cell viability to 40-60% after 72 h in both cell lines. Additionally, the annexin V-positive rate and sub-G0/G1 phase population were significantly elevated in HEp-2 cells (mock vs GALR2: 12.3 vs 25.0% (P < 0.01) and 9.1 vs 32.0% (P < 0.05), respectively) after 48 h. These changes were also observed in KB cells, although to a lesser extent. Furthermore, in HEp-2 cells, GALR2-mediated apoptosis was caspase-independent, involving downregulation of ERK1/2, followed by induction of the pro-apoptotic Bcl-2 protein, Bim.

  • Research Products

    (5 results)

All 2014 2012 Other

All Journal Article (2 results) Presentation (3 results)

  • [Journal Article] Novel anti-tumor mechanism of galanin receptor type 2 in head and neck squamous cell carcinoma cells2014

    • Author(s)
      Uehara T, Kanazawa T, Mizukami H, Uchibori R, Tsukahara T, Urabe M, Kume A, Misawa K, Carey TE, Suzuki M, Ichimura K, Ozawa K
    • Journal Title

      Cancer Sci

      Volume: 105 Pages: 72-80

  • [Journal Article] Galanin Receptor 2 Utilizes Distinct Signaling Pathways to Suppress Cell Proliferation and Induce Apoptosis in HNSCC

    • Author(s)
      Kanazawa T, Misawa K, Misawa Y, Maruta M, Uehara T, Kawada K, Nagatomo T, Ichimura K
    • Journal Title

      Mol Med Rep

      Volume: (in press)

  • [Presentation] 頭頸部扁平上皮癌におけるガラニン受容体2型を介する新たな抗腫瘍機構の解明2012

    • Author(s)
      上原貴行,金澤丈治,水上浩明,内堀亮介,塚原智典,卜部匡司,久米晃啓,三澤清,小澤敬也
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Year and Date
      20120919-21
  • [Presentation] Galanin受容体2型導入による頭頸部癌遺伝子治療研究2012

    • Author(s)
      金澤丈治,上原貴行,三澤清,鈴木幹男,市村恵一
    • Organizer
      第36回日本頭頸部癌学会総会・学術講演会
    • Place of Presentation
      松江
    • Year and Date
      20120607-08
  • [Presentation] アデノ随伴ウイルスベクターを用いたガラニン受容体2型遺伝子導入による抗腫瘍効果の検討2012

    • Author(s)
      上原貴行,金澤丈治,市村恵一,鈴木幹男
    • Organizer
      第113回日本耳鼻咽喉科学会総会・学術講演会
    • Place of Presentation
      新潟
    • Year and Date
      20120510-12

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Published: 2015-07-16  

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