| Project/Area Number |
18591836
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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 | Kyushu University |
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Principal Investigator |
MIBU Ryuichi Kyushu University, Faculty of Medicine, Professor (20200107)
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| Co-Investigator(Kenkyū-buntansha) |
KATO Kiyoko Kyushu University, Medical Institute of Bioregulation, Lecturer (10253527)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,920,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2006: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | MPA / Hormone Replacement Therapy / Colorectal Cancer / 更年期医学 / 消化器学 |
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| Research Abstract |
Numerous epidemiological and experimental studies have suggested the possible effect of female sex hormones against colon cancer risk. The Women's Health Initiative recently reported data from a randomized controlled trial that compared estrogen plus progestin with placebo in postmenpausal women. In this report, therapy with a combination of conjugated equine estrogen(CEE) plus MPA was associated with a significant decrease in the incidence of colorectal cancer, while therapy with CEE alone neither increased nor decreased the incidence of colorectal cancer. However, the precise mechanism by which MPA prevents colorectal cancer remains to be fully investigated. To investigate the effects of medroxyprogesterone acetate on colon cancer cells in vitro, HT29 and HCT116 human colon cancer cell lines were used in this study. Cell growth and WST-1 assays were performed to investigate the antiproliferative effect of medroxyprogesterone acetate. Cell cycle analysis was performed to investigate the effects of medroxyprogesterone acetate on cell cycle distribution. Western blot, immunoprecipitation and cyclin-dependent kinase assay were performed to investigate changes in the levels of cell cycle proteins.
Medroxyprogesterone acetate inhibited proliferation of the cancer cells by inducing accumulation in the G0/G1 fraction. Medroxyprogesterone acetate decreased expression of cyclin E, increased expression of p21, and enhanced interaction of p21 with cyclin-dependent kinase2, eventually inhibiting its activity. Medroxyprogesterone acetate exerts its antiproliferative effect by modulating cell cycle-related protein expression and cyclin-dependent kinase 2 activity. These results should help to elucidate the protective effect of medroxyprogesterone acetate on colon cancer risk.
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