2017 Fiscal Year Final Research Report
Clinical study of endometrial cancer prevention by metformin: targeting obesity and insulin resistance
| Project/Area Number |
15K10702
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Chiba University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
生水 真紀夫 千葉大学, 大学院医学研究院, 教授 (30226302)
植原 貴史 国立研究開発法人国立がん研究センター, 中央病院, 医員 (70568659)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | 子宮体癌 / 肥満 / インスリン抵抗性 / メトホルミン |
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| Outline of Final Research Achievements |
bnormal glucose metabolism, insulin resistance, and obesity were found to be highly prevalent in patients with endometrial cancer and atypical endometrial hyperplasia. Protein phosphatase 2A (PP2A) is a serine/threonine phosphatase that is associated with insulin resistance and type 2 diabetes. Preoperative metformin treatment significantly reduced PPP2R4 mRNA expression in endometrial cancer tissues and immunohistochemistry showed significantly decreased expression of the PP2A-β subunit. PPP2R4 knockdown reduced cell proliferation and induced apoptosis in HEC265 and HEC1b cells by activating caspases 3/7. Metformin inhibited the growth of endometrial cancer cells in vivo by indirectly down-regulating PP2A-β and PPP2R4. Inhibition of PP2A may become a preventive measure and a therapeutic strategy for endometrial cancer with insulin resistance.
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| Free Research Field |
婦人科腫瘍
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