| Project/Area Number |
24791696
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Shinshu University |
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Principal Investigator |
ASAKA Ryoichi 信州大学, 医学部附属病院, 医員 (00623688)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | Sirtuin1 / 子宮内膜癌 / シスプラチン耐性 / SIRT1阻害剤 / EX527 / 長寿遺伝子 / 脱アセチル化 / p53 / 増殖能 |
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| Research Abstract |
The immunohistochemical expression of Sirtuin1 (SIRT1) was significantly higher in endometrial carcinoma (108 cases) than in normal endometria (60 cases) (p<0.05), and its overexpression was associated with a shorter survival (p<0.05). The WST-1 assay revealed that SIRT1 accelerated the proliferation and cisplatin resistance of endometrial carcinoma cell lines (HHUA, HEC151 and HEC1B). Whereas the selective SIRT1 inhibitor (EX527) suppressed the proliferation and cisplatin resistance of those cell lines regardless of the
p53 mutation. The effects of SIRT1 on tumor growth were examined in vivo using mice xenografts of HHUA and HEC1B cells. SIRT1 overexpression significantly increased tumor growth, however, EX527 significantly suppressed tumor growth in nude mice. In conclusion, SIRT1 is involved in the acquisition of the aggressive behavior associated with endometrial carcinoma, and the SIRT1 inhibitor, EX527, may be a useful agent for the treatment of this malignancy.
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