2003 Fiscal Year Final Research Report Summary
Sensitization of cancer cells to anti-cancer drugs by the integrin function-suppressing peptide FNIII14.
| Project/Area Number |
14572100
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
医薬分子機能学
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| Research Institution | Tokyo University of Science |
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Principal Investigator |
HUKAI Humio Tokyo University of Science, Faculty of Pharmaceutical Sciences, Assistant professor, 薬学部, 助教授 (90124487)
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| Project Period (FY) |
2002 – 2003
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| Keywords | anticancer drug / integrin / fibronectin / adhesion / cell death / apoptosis / extracellular marti* / anoikis |
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| Research Abstract |
We have found that the ability of actinomycin D to induce programmed death of murine melanoma cells B16BL6markedly increases when cell adhesion to fibronectin(FN)is weakened ny a FN-derived antiadhesive peptide FNIIII4.In this study, we investigated the effects of FNIII 14 on cytotoxic activity of the other anticancer drugs and also the mechanism by which FNIIII4 sensitizes B16BL6 cells to anticancer drugs.Results demonstrated as follows :
1)FNIII14 negatively regulates the activation of bi integrins also in adherent cell types.
2)Increased susceptibility ofB16BL6 cells to anticancer drugs by FNIIII4 is highly remarkable using drugs targetting to microtubles such as pacrytaxicel, vinblastin, and vincrystin, in which the LD50 values of these drugs to cells in the presence of FNIIIl4 are 1/100-1/10000 lower than those in the absence of FNIII 14.
3)FNIII14 suppresses the activation of Akt in response to adhesion to FN, resulting in suppression of the antiapoptotic protein Bcl-2 expression.
Dr.Niitsu and his collaborators recently found that acute myelocytic leukemia cells aquire chemoresistancy against anticancer drugs through adhesion to bone marrow stroma EN matix via integrin a4b land that this interaction is closely correlated to minimal residual disease(MRD)of AML Since our prptide FNlIII4 is also capable of abrogating the a4b 1-mediated interaction, it would be expected that FNIII14 could be practically used as an effective drug to prevenmt MRD.
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[Publications] Kamiya, S., Kato, R., Goto, S., Fukai, F.: "Extracellular matrix proteins as signal trabsduction factors in Cell regulation through the extracellular matrix-integrin system."Recent Research Development in Biophysics & Biochemistry,(Pandalai, S.G.,Ed.). 103-119 (2003)
Description
「研究成果報告書概要(和文)」より
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