| Project/Area Number |
15K10699
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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 | Yamagata University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
鈴木 史彦 東北大学, 医学系研究科, 助教 (20400343)
太田 剛 山形大学, 医学部, 講師 (50375341)
清野 学 山形大学, 医学部, 助教 (40594320)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 子宮体部漿液性癌 / メタボローム解析 / パクリタキセル耐性 / スルファサラジン / フェロトーシス / 子宮体部漿液性腺癌 / 抗がん剤耐性 / パクリタキセル |
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| Outline of Final Research Achievements |
First, we examined metabolomic profile in USC cells by analysis using a capillary electrophoresis CE-MS/MS system. The concentration of GSH, Glucose-6-phosphate and ribose-5-phasphate in the PTX-1 cells was higher than that of USPC-1 cells. Next, we investigated the effect of the xCT inhibitor sulfasalazine (SAS) on cytotoxicity in paclitaxel-sensitive and -resistant USC cell lines. The results of proliferation and cell-death assays showed that SAS enhanced the efficacy of paclitaxel in both paclitaxel-sensitive and -resistant cell lines. Immunoblotting analysis and experiments conducted using ferroptosis inhibitors revealed that SAS-mediated cell death was induced through ferroptosis, and not apoptosis, in paclitaxel-resistant cells. Collectively, our findings indicate that xCT inhibition can overcome resistance to paclitaxel, and could thus represent a candidate novel treatment for patients with recurrent chemotherapy-resistant USC.
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