2014 Fiscal Year Final Research Report
Molecular mechanism on the drug resistance and responsiveness against anticancer agents and molecular-target agents
| Project/Area Number |
23300364
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Clinical oncology
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| Research Institution | Keio University |
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Principal Investigator |
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| Project Period (FY) |
2011-04-01 – 2015-03-31
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| Keywords | ABCトランスポーター / ABCB1 / ABCG2 / ABCB5 / P-糖タンパク質 / BCRP / 抗がん剤耐性 |
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| Outline of Final Research Achievements |
The main results of this research project are as follows: (1) The ABCB5 transfectants showed resistance to various anti-cancer agents including docetaxel. Cellular uptake of radiolabeled docetaxel in the transfectants was lower than that in the parental cells, suggesting that ABCB5 mediates the efflux of these anticancer agents. (2) Ubiquitin E3 ligase FBXO15 and ubiquitin-conjugating enzyme UBE2R1 cooperatively ubiquitinated P-glycoprotein and promoted its degradation. (3) Protein phosphatase complex PP5/PPP2R3C negatively regulated the expression and function of P-glycoprotein. (4) A novel acrylonitrile derivative enhanced the antitumor activity of CPT-11 in a xenograft model of BCRP-expressing human colon cancer without a remarkable increase in body weight loss.
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| Free Research Field |
分子細胞生物学
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