| Project/Area Number |
08672607
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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 |
応用薬理学・医療系薬学
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| Research Institution | KOBE UNIVERSITY |
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Principal Investigator |
TANIGAWARA Yusuke Kobe University, University Hospital Faculty of Medicine, Associate Professor, 医学部・附属病院, 助教授 (30179832)
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| Co-Investigator(Kenkyū-buntansha) |
OKUMURA Katsuhiko Kobe Univesity, University Hospital Faculty of Medicine, Professor, 医学部・附属病院, 教授 (60025707)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1997: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1996: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | P-glycoprotein / Multidrug resistance / Transport / Pharmacokinetics / Anticancer agents / Chemosensitizer / chemosensitizer / doxorubicin / docetaxel / SDZ PSC-833 |
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| Research Abstract |
Multidrug resistance (MDR) is a major obstacle in cancer chemotherapy. One of important mechanisms of MDR is P-glycoprotein (P-gp) which actively expels anticancer drugs out of the cells and decreased their intracellular concentration, resulting in the resistance aganinst multiple agents. Modulation of P-gp can reverse the MDR and many improve outcome of cancer chemotherapy.
1. SDZ PSC 833, a non-immunosuppressive cyclosporin derivative, was 5-to 10-fold more potent to reverse multidrug resistance compared to cyclosporin A.This is probably because PSC 833 is not transported by human P-gp and is more hydrophobic than Cs-A.
2. Transport activity in the MDR-transfected cells was well correlated with the expression level of P-gp protein.
3. Docetaxl, a new anticancer agent, was a substrate transported by P-gp.
4. Itraconazole inhibited the P-gp mediated transport of digoxin, suggesting a mechanism of clinically important digoxin-itraconazole interaction. Itraconazole also reversed sensitivity to vinblastine in the P-gp expressed cells.
5. Inhibitory effect of various Ca^<2+> antagonists on digoxin transport via P-gp was related to the molecular weight of Ca^<2+> antagonists.
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