| Project/Area Number |
25462481
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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 |
Urology
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| Research Institution | Yamaguchi University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
MATSUYAMA Hideyasu 山口大学, 大学院医学系研究科, 教授 (70209667)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | 腎細胞がん / AMPK / メトホルミン / mTOR阻害剤 / チロシンキナーゼ阻害剤 / 併用療法 / エベロリムス / mTOR経路 |
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| Outline of Final Research Achievements |
To conquer drug-resistance of renal cell carcinoma, we tried to establish a new therapeutic strategy through AMPK/mTOR pathway and assessed the synergy effect combined with molecular targeted drug and metformin. In renal cancer cell lines, Everolimus, Axitinib and Metformin repressed the cell growth in dose dependent manner. As a result, Metformin showed high growth inhibitory effect in each cell lines. In particular, Metformin did not only show synergistic apoptosis effect in combination with Axitinib, but also enhanced AMPK expression and suppressed mTOR expression. In the mouse model, combination of Metformin and each single agent showed synergistic tumor growth inhibition, decreased micro-vessel density and repressed the expression of VEGF in tumor tissue.
These results suggest that combination treatment of Metformin and molecular targeting for AMPK/mTOR pathway shows pre-clinical proof of principal as a new therapeutic strategy for renal cell carcinoma.
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