2006 Fiscal Year Final Research Report Summary
Study on aiming to use of clofibrate as an anticancer agent
| Project/Area Number |
16591632
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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 |
Obstetrics and gynecology
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| Research Institution | Hirosaki University |
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Principal Investigator |
YOKOYAMA Yoshihito Hirosaki University, School of Medicine, Assistant professor, 医学部, 講師 (90261453)
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| Co-Investigator(Kenkyū-buntansha) |
MIZUNUMA Hideki Hirosaki University, School of Medicine, Professor, 医学部, 教授 (10125875)
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| Project Period (FY) |
2004 – 2006
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| Keywords | Clofibric acid / Ovarian cancer / Prostaglandin E2 / Carbonyl reductase / Angiogenesis / Apoptosis / Antitumor effect / CDDP |
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| Research Abstract |
Recent reports have demonstrated that peroxisome proliferator-activated receptor (PPAR)α ligands reduce growth of some types of malignant tumors and prevent carcinogenesis. In this study, we investigated the inhibitory effect of clofibric acid (CA), a ligand for PPARα on growth of ovarian malignancy in in vivo and in vitro experiments using OVCAR-3 and DISS cells derived from human ovarian cancer and aimed to elucidate the molecular mechanism of its antitumor effect. CA treatment significantly suppressed the growth of OVCAR-3 tumors xenotransplanted subcutaneously and significantly prolonged survival of mice with malignant ascites derived from DISS cells as compared to control. CA also dose-dependently inhibited cell proliferation of cultured cell lines. CA treatment increased expression of carbonyl reductase (CR), which promotes conversion of prostaglandin (PG) E_2 to PGF_<2_α>, in implanted OVCAR-3 tumors as well as cultured cells. CA treatment decreased PGE_2 level as well as vascular endothelial growth factor (VEGF) amount in both of OVCAR-3-tumor and DISS-derived ascites. Reduced microvessel density and induced apoptosis were found in solid OVCAR-3 tumors treated by CA. Transfection of CR expression vector into mouse ovarian cancer cells showed significant reduction of PGE_2 level as well as VEGF expression. These results indicate that CA produces potent antitumor effects against ovarian cancer in conjunction with reduction of angiogenesis and induction of apoptosis. We conclude that CA could be an effective agent in ovarian cancer and should be tested alone and in combination with other anticancer drugs.
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