2006 Fiscal Year Final Research Report Summary
Analyses of biological effects of Statin on the growth of human prostate cancer cells
| Project/Area Number |
17591684
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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 |
Urology
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| Research Institution | Nagasaki University |
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Principal Investigator |
IGAWA Tsukasa Nagasaki University, Graduate School of Biomedical Sciences, Research Associate (40295069)
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| Co-Investigator(Kenkyū-buntansha) |
SAKAI Hideki Nagasaki University, Hospital of Medicine and Dentistry, Assistant Professor (40235122)
KANETAKE Hiroshi Nagasaki University, Graduate School of Biomedical Sciences, Professor (50100839)
MIYATA Yasuyoshi Nagasaki University, Graduate School of Biomedical Sciences, Research Associate (60380888)
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| Project Period (FY) |
2005 – 2006
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| Keywords | Prostate cancer / Statin / PC-3 cells / Small G protein / RhoA / Rac-1 |
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| Research Abstract |
OBJECTIVES: Several lines of evidence demonstrate that HMG-CoA reductase inhibitor (Statin) use may be associated with reduced risks of some kinds of human cancers including prostate cancer. However, the precise mechanism of statin effects on the behavior of human prostate cancer cells remained to be elucidated. Thus we analyzed the biological effects of statin and explored the biological role in human prostate cancer cells.
RESULTS:
1. Effects of different statin on the growth of prostate cancer cells
The growth of different PCa cells, i. e. LNCaP, PC-3 and DU-145 cells, have been apparently suppressed by different statin including Pravastatin, Fluvastatin and Simvastatin. The suppression effect was strongest by Simvastatin, and weakest by Pravastatin.
2. Effects of different statin on the cell motility of prostate cancer cells
Similar to the results of growth inhibitory effects, cell motility of PC-3 cells was inhibited by each statin using transwell assay. Simultaneously, we investigated the protein expression levels of small G protein including RhoA and Rac-1. Under the stimulation of statin, the phosphorylation level of Rac-1 has been decreased dose-dependently. On the other hand, the level of RhoA has been increased.
3. The role of p38MAPK on the secretion of IL-6 by PC-3 prostate cancer cells
The androgen independent growth of PC-3 and DU145 cells was mediated by stress-activated protein kinases (SAPKs) including p38MAPK and JNK IL-6 secretion by PC-3 cells was significantly suppressed by SAPKs inhibitor, especially by p38MAPK inhibitor; SB203580.
CONCLUSIONS:
1. Statin negatively regulate the cell growth as well as cell motility of prostate cancer cells. This effect may be exhibited by the changes of the activities of small G protein including RhoA and Rac-1.
2. IL-6 mediated androgen-independent proliferation of PC-3 and DU145 cells is regulated at least partly via SAPKs signaling pathway especially through p38MAPK activation.
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