Prevention of hepatic carcinogenesis and treatment of hepatoma by way of inhibition of the activation of Ras oncogene
| Project/Area Number |
07670599
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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 |
Gastroenterology
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| Research Institution | Kyushu University |
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Principal Investigator |
SAKAI Hironori Kyushu University・Faculty of Medicine, Assist.Prof., 医学部, 講師 (70196046)
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| Co-Investigator(Kenkyū-buntansha) |
ISOBE Hidehiko Kyushu University・Faculty of Medicine, Assist.Prof., 医学部, 助手 (60253407)
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| Project Period (FY) |
1995 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1997: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1996: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1995: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | Ras Protein / HMG-CoA Reductase Inibiter / Hepatoma / 肝細胞癌 / ras蛋白 / HMG-CoA reductase阻害剤 / メバロン酸 |
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| Research Abstract |
HMG-CoA reductase inhibiters inhibit the mevalonic pathway and then regulate the function of Ras protein. We tried to exhibit that they were able to inhibit the growth of hepatocyte and some kinds of hepatoma cell lines and that they had the possible therapeutic effect on hepatocellular carcinoma.
1. Simvastasin inhibited the growth of hepatoma cell lines (Hep G2, HuH-7, HLE, PLC/PRF/5) as a dose dependent manner. The extents of inhibition of growth were all most same among these cell lines.
2. Pravastatin did not have inhibitory effects of growth of all these cell lines. Since hepatoma cell lines did not have anion transporter system to transfer pravastatin into cells, pravastatin failed to inhibit the growth of these cells.
3. The inhibitory effect of simvastatin on hepatoma cell growth was nearly prevented in the presence of sufficient amount of exogenous mevalonic acid. So it was obvious that the mevalonic pathway was required for the growth of these cell lines. But neither farnesol nor isopentenyl adenine prevented the simvastatin induced inhibition of the growth of these cell lines.
4. Clinical trial of HMG-CoA reductase inhibiter administrated to patients with hepatocellular carcinoma revealed that simvastatin possibly had a therapeutic effects but pravastatin did not have.
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Report
(4 results)
Research Products
(1 results)
