| Project/Area Number |
24592036
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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 |
Digestive surgery
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| Research Institution | Nagoya City University |
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Principal Investigator |
TAKAHASHI Hiroki 名古屋市立大学, 医学(系)研究科(研究院), 講師 (30381792)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUO Yoichi 名古屋市立大学, 医学(系)研究科(研究院), 准教授 (40381800)
HARA Masayasu 名古屋市立大学, 医学(系)研究科(研究院), 講師 (80528860)
SATO Mikinori 名古屋市立大学, 医学(系)研究科(研究院), 講師 (20305551)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 膵臓癌 / アポトーシス / Bcl-2ファミリー蛋白 / RNA干渉 |
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| Outline of Final Research Achievements |
Of all gastrointestinal carcinomas, pancreatic cancer (PaCa) has the most unfavorable prognosis. Anti-apoptotic members of the Bcl-2 protein family are often over-expressed in human cancers and are thought to mediate the resistance to chemotherapeutic drugs. Thus, a better understanding of the anti-apoptotic mechanisms and the development of potent and non-toxic strategies to overcome the pro-survival mechanisms in PaCa cells are of utmost importance to improve the outcome of PaCa patients.
In this reseach, we first showed that the expression and localization of anti-apoptotic Bcl-2 family proteins in PaCa cells. Then, we used siRNA targeting to Bcl-2, Bcl-xL, and Mcl-1 to confirm the importance of anti-apoptotic Bcl-2 family proteins in PaCa cell survival. Simultaneous knock-down of Bcl-xL and Mcl-1 induced apoptosis strongly through Bax/mitochondria pathway. These results suggest that Bcl-xL and Mcl-1, which are over-expressed in PaCa may be potential therapeutic targets.
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