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Basic research on anti-tumor effects of Interferon-α on hepatocellular carcinoma

Research Project

Project/Area Number 13670233
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionKURUME UNIVERSITY

Principal Investigator

YANO Hirohisa  Kurume University, School of Medicine, Associate Professor, 医学部, 助教授 (40220206)

Co-Investigator(Kenkyū-buntansha) MASAMICHI Kojiro  Kurume University, School of Medicine, Professor, 医学部, 教授 (90080580)
OGASAWARA Sachiko  Kurume University, School of Medicine, Fellow, 医学部, 助手 (40258405)
MOMOSAKI Seiya  Kurume University, School of Medicine, Instructor, 医学部, 講師 (40279138)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2003: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2002: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2001: ¥1,400,000 (Direct Cost: ¥1,400,000)
KeywordsHepatocellular carcinoma / Interferon-α / Apoptosis / Caspase / Cell line / Nude mouse / 5-Fu / Interferon-α subtypes / インターフェロン-α / コンセンサスインターフェロン / アポトーシス / ヌードマウス / 血管新生 / 抗癌剤 / 肝癌 / 細胞株 / カスペース(caspase) / cytochrome c / RT-PCR / Western blotting / インターフェロン-αサブタイプ / 増殖抑制
Research Abstract

[Purpose] In this study, we examined that the effects of IFN-α subtypes on the growth of human liver cancer cell lines in vitro ; growth inhibitory effects of IFN-α and 5-Fu in vitro ; mechanisms of apoptosis induction by IFN-α; and the effects of IFN-α alone or IFN-α plus 5-Fu on the growth of human liver cancer cell lines transplanted In nude mice.
[Results] 1. When we examined the effects of five kinds of recombinant IFN-α subtypes (α1, α2, α5, α8, α10; concentrations: 0-1024 IU/mL; 24-96 hours) on the growth of 13 human liver cancer cell lines, the strongest anti-proliferative effects was noted In IFN-α5 subtype, and followed by α8, α10, α2, α1. 2. No synergistic growth Inhibitory effects could be recognized when IFN-α and 5-Fu were simultaneously added t o the culture of liver cancer cells. 3. Natural human IFN-α induced activation of caspase-3, -7, -8, and -9, and proteolysis of PARP in IFN-α-induced apoptosis-sensitive cell lines at various degrees. In addition, release of cytochrome C and Smac/Diablo from mitochondria into cytoplasm was identified in IFN-α-treated cells time-dependently. These findings suggest mitochondria apoptosis induction pathway is involved in the IFN-α-induced apoptosis. 4. Subcutaneous IFN-αCon1 injection (0.01, 0.1, 1μg/mouse/day; 0.01 μg/mouse = clinical dosesage) for consecutive 14 days dose-and time-dependently suppressed the HCC tumor growth in nude mice. Finally, the tumor volumes of mice received 0.01, 0.1, and 1 μg/mouse of IFN-αCon1 decreased to about 60%, 25%,and 0-10%, respectively, of control tumor volumes. The number of apoptotic cells significantly Increased and the number of blood vessels significantly decreased with the increase of IFN-αCon1 dose. 5. Synergistic effect of IFN-α plus 5-Fu was identified In nude mouse tumors. [Conclusions] These data Indicate the potential clinical application of certain types of IFN-α in the prevention and treatment of HCC.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] 矢野博久, 神代正道: "インターフェロンは培養肝癌細胞増殖を抑制する"医学と薬学. 47巻・supple. 69-74 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 矢野博久, 神代正道: "IFNの代謝-抗腫瘍作用"肝胆膵. 45巻・6号. 1001-1006 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 矢野博久: "IFNの肝癌細胞に対する直接的な増殖抑制作用"Frontiers in Gastroenterology. 9・1. 87-89 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hisaka T, Yano H, et al.: "Interferon-α Con1 suppresses proliferation of liver cancer cell lines in vitro and in vivo."Journal of Hepatology. (In press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yano, H: "Interferon Inhibits proliferation of livercancer cell lines in vitro"Jpn J Med Pharm Sci. vol 47(supple). 69-74 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yano, H: "anti-tumor action of IFN"kan-tan-sui. vol 45,No.6. 1001-1006 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yano, H: "Direct growth Inhibitor effects of IFN on liver cancer cells"Frontiers In Gstroenterology. vol9,No 1. 87-89 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hisaka, T: "Interferon-aCon1 suppresses proliferation of liver cancer cell lines in vitro and in vivo"J.Hepatol.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yano H et al.: "Consensus interferon (interferon-alphaCon1) inhibits the growth of liver cancer cell lines in vitro and in vivo"Hepatology. 38・4・supple. 599A (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 矢野博久: "IFNの肝癌細胞に対する直接的な増殖抑制作用"Frontiers in Gastroenterology. 9・1. 87-89 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 矢野博久, 神代正道: "インターフェロンは培養肝癌細胞増殖を抑制する"医学と薬学. 47巻・supplement. 69-74 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 矢野博久, 神代正道: "IFNの代謝-抗腫瘍作用"肝胆膵. 45巻・6号. 1001-1006 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 矢野博久, 神代正道: "インターフェロンは培養肝癌細胞増殖を抑制する"医学と薬学. 47 supplement(印刷中). (2002)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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