2004 Fiscal Year Final Research Report Summary
Effect of cyclooxygenase-2 and lipoxygenase on progression of prostate cancer
| Project/Area Number |
15591676
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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 | Kanazawa University |
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Principal Investigator |
MIZOKAMI Atsushi Kanazawa University, Hospital, Lecturer, 医学部附属病院, 講師 (50248580)
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| Co-Investigator(Kenkyū-buntansha) |
NAMIKI Mikio Kanazawa University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (70155985)
KOSHIDA Kiyoshi Kanazawa University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 助教授 (70186667)
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| Project Period (FY) |
2003 – 2004
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| Keywords | COX-2 / prostate cancer / lipoxygenase |
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| Research Abstract |
We ligated VEGF promoter of various length in upstream of luciferase gene, transfected these in LNCaP cells, and added PGE2 which was metabolic product by COX-2, and examined VEGF promoter activity.
The clear inductive activity was not recognized by PGE2. Next we transfected the vector which joined luciferase gene together in PSA promoter in LNCaP-neo and COX-2 overexpression cell line LNCaP-COX-2, and we added 10-8 M DHT and measured PSA promoter activity. The responsiveness for DHT fell with COX-2 overexpressed cell line. It was suggested that prostate cancer cells become androgen-independent via reduced androgen-responsiveness when COX-2 was overexpressed, in prostatic cancer.
When prostate cancer cells were treated with arachidonic acid that was related with fatty acid metabolism, the cell proliferation was stimulated. In order to investigate which metabolites from arachidonic acid are involved in, we examined the effects of COX-2 inhibitors and LOX inhibitors on the proliferation. These inhibitors inhibited the proliferation of irrespective of arachidonic acid, suggesting that arachidonic acid just acts as essential nutrition.
We also investigated that sensitivity against anti-cancer drug in COX-2 overexpressing cells. The sensitivity against cisplatin was reduced in COX-2 overexpressing cells. MRP2 induction by COX-2 was involved in this mechanism.
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