1996 Fiscal Year Final Research Report Summary
A Study of Farnesyltransferase Inhibitor for the Treatment of Pancreatic Cancer.
| Project/Area Number |
07671290
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Chiba University |
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Principal Investigator |
ASANO Takehide Chiba University, School of Medicine Lecturer, 医学部, 講師 (80143311)
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| 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
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| Project Period (FY) |
1995 – 1996
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| Keywords | Farnesyltransferase inhibitor / Manumycin / Pancreatic cancer / MAPK / Ras |
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| 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.
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