| Project/Area Number |
25861491
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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 | Osaka University |
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Principal Investigator |
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 婦人科腫瘍 / 子宮平滑筋肉腫 / プラチナ耐性 / プラチナトランスポーター / 化学療法抵抗性 |
|---|
| Outline of Final Research Achievements |
In this study, we investigated the role of ATP7A and ATP7B in uterine leiomyosarcoma (LMS) cells which had high level expression of ATP7A and ATP7B. In LMS cell lines, knockdown the expression of ATP7A and ATP7B improved the sensitivity of Cisplatin in vitro. Compared with control LMS cells, knockdown of ATP7A and ATP7B induced roughly 4-fold greater chemosensitization to Cisplatin (IC50: 17.0 μM to 6.1 μM, 4.3 μM respectively; p<0.01) To elucidate the mechanism underlying platinum resistance induced by ATP7A and ATP7B, intracellular platinum accumulation of LMS control cells, LMS silencing ATP7A cells and ATP7B cells after Cisplatin exposure were analyzed. Significantly increased platinum had accumulated in LMS silencing ATP7A and ATP7B cells compared with LMS control cells (p < 0.01). Thus, intracellular platinum accumulation was increased in LMS silencing ATP7A cells and ATP7B cells. To perform further investigation, we generate stable ATP7A and ATP7B knockdown cell lines.
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