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A Study of Farnesyltransferase Inhibitor for the Treatment of Pancreatic Cancer.

Research Project

Project/Area Number 07671290
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionChiba University

Principal Investigator

ASANO Takehide  Chiba University, School of Medicine Lecturer, 医学部, 講師 (80143311)

Co-Investigator(Kenkyū-buntansha) ISONO Kaichi  Chiba University, School of Medicine Professor, 医学部, 教授 (70009489)
KENMOCHI Takashi  Chiba University, School of Medicine Hospital Assistant, 医学部・附属病院, 助手 (50215133)
KAINUMA Osamu  Chiba University, School of Medicine Hospital Instructor, 医学部・附属病院, 医員
中郡 聡夫  千葉大学, 医学部・附属病院, 助手 (10261918)
植松 武史  千葉大学, 医学部・附属病院, 助手 (00251158)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1996: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1995: ¥1,100,000 (Direct Cost: ¥1,100,000)
KeywordsFarnesyltransferase inhibitor / Manumycin / Pancreatic cancer / MAPK / Ras / farnesyltransferase inhibitor / manumycin / apoptosis / K-ras
Research Abstract

The effects of manumycin, a competitive farnesyltransferase (FTase) inhibitor, on pancreatic cancer cell lines with or without K-ras mutation were studied. Manumycin inhibited the growth of human pancreatic cancer cells (SUIT-2, MIA PaCa-2, AsPC-1, BxPC-3) in a dose-dependent manner. The fifty percent inhibitory concentration (IC_<50>) in cell lines with a mutant K-ras gene (SUIT-2, MIA PaCa-2, AsPC-1) was lower than that in BxPC-3 with a wild-type ras. Both mitogen-activated protein kinase (MAPK) activity after growth stimuli and an ability of chemotactic invasion were markedly inhibited by manumycin in SUIT-2 than in BxPC-3. These results suggest that mutated Ras is more sensitive to manumycin than wild-type. Futhermore, tumor growth and liver metastasis in nude mice inoculated with manumycin-treated SUIT-2 cells were inhibited dose-dependently. Thus, this study provides evidence that Manumycin inhibits growth and invasiveness of human pancreatic cancer cells by inhibition of signal transduction. This result suggests that manumycin is potentially useful for the treatment of pancreatic cancer. Inhibition of Ras activity might be a new anti-cancer strategy in pancreatic cancer in which Ras plays a role.

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (3 results)

All Other

All Publications (3 results)

  • [Publications] 貝沼修: "ファルネシア化阻害剤による膵癌治療の可能性" 癌と化学療法. 23. 1657-1659 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Osamu Kainuma, Takehide Asano, Masayuki Hasegawa, and Kaichi Isono: "Growth Inhibition of Human Pancreatic Cancer by Farnesyl Transferase Inhibitor" Jpn J Cancer Chemother. 23. 1657-1659 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 貝沼修: "ファルネシル化阻害剤による膵癌治療の可能性" 癌と化学療法. 23. 1657-1659 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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