2017 Fiscal Year Final Research Report
A developmental research for a novel MDM4-targeted anti-cancer therapy
| Project/Area Number |
15K19160
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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 |
Applied pharmacology
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| Research Institution | University of Tsukuba |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | MDM4 / MDM2 / siRNA / dsRDC / p53 / Trametinib / KRAS変異 |
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| Outline of Final Research Achievements |
In TP53 wild-type tumors, MDM4 and MDM2 promote tumor progression by not only down-regulation of p53 but also interactions with molecular of MAPK pathway. In this study, we aim to evaluate the combination effects of double-stranded RNA-DNA chimera (dsRDC)-modified siRNAs targeting MDM4 and MDM2, and MEK inhibitor (Trametinib). At first, the combination of these 3 drugs showed the potent synergistic effects on MDM4 overexpressed TP53 wild-type, and RAS mutant cancer cell lines. In addition, this triple-drug combination induced apoptosis and cell cycle arrests (G1 and G2 arrests). Further studies are needed to reveal the mechanism of this synergistic effect.
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| Free Research Field |
消化器内科
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