Reversal Effects of Antifungal Drugs on Multidrug Resistance in MDR1-Overexpressing HeLa Cells
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概要
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In this study, the antiproliferative effects of vinblastine(VLB), paclitaxel(TXL), doxorubicin(DXR), daunorubicin(DNR)and 5-fluorouracil(5-FU)were assessed in the human carvical carcinoma cell line HeLa-Ohio(HeLa)and Hvr100-6 cells, established by growing the parental HeLa cells in the presence of progressively greater concentrations of VLB in the culture medium. Flow cytometric analysis indicated the induction of MDR1(P-glycoprotein)in Hvr100-6 cells with no alterations in levels of multidrug resistance-associated protein(MRP). Resistance to VLB, TXL, DXR and DNR was found in Hvr100-6 cells with relative resistances of ca.300, 4000, 50 and 200, respectively, whereas no resistance was found to 5-FU. The reversal effects of antifungal drugs, fluconazole, itraconazole, ketoconazole, miconazole and amphotericin B on multidrug resistance were also assessed using Hvr100-6 cells. Itraconazole was found to have potent reversal effect on the resistance to VLB and TXL, but the others had no such effect. This reversal effect of itraconazole was concentration-dependent, with dose modifying factors of 3.2, 10.1 and 435.7 at 0.1, 0.25 and 0.5μM of itraconazole, respectively. In addition, this reversal effect of itraconazole was explained by the inhibition of accumulation of the anticancer drugs.
- 2001-09-01
著者
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Kimura Takashi
Department of Neurology, National Douhoku Hospital
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HIRAI Midori
Department of Clinical Pharmacy, Kobe Pharmaceutical University
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Nakamura T
Department Of Gastroenterological Surgery Kobe University Graduate School Of Medical Sciences
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NAKAMURA Tsutomu
Department of Hospital Pharmacy, Kobe University School of Medicine
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OKUMURA Katsuhiko
Department of Hospital Pharmacy, Kobe University School of Medicine
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SAKAEDA Toshiyuki
Department of Hospital Pharmacy, Kobe University School of Medicine
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Kimura T
Kobe University Graduate School Of Medicine
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Kamigaki T
Kobe Univ. School Of Medicine Kobe
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Hirai M
Kobe Pharmaceutical University
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Hirai M
Kobe Pharmaceutical Univ.
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Ohmoto Nobuko
Department of Hospital Pharmacy, School of Medicine, Kobe University
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Takara Kohji
Department of Hospital Pharmacy, Faculty of Pharmaceutical Sciences, Kyoto Pharmaceutical University
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WADA Atsushi
Department of Clinical Pharmacy, Kobe Pharmaceutical University
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Okumura K
Department Of Clinical Evaluation Of Pharmacotherapy Kobe University Graduate School Of Medicine
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Wada A
Department Of Hospital Pharmacy School Of Medicine Kobe University
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Wada Atsushi
Department Of Cardiovascular Medicine Chigasaki Municipal Hospital
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Takara Kohji
Department Of Hospital Pharmacy Faculty Of Pharmaceutical Sciences Kyoto Pharmaceutical University
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Takara Kohji
Department Of Clinical Pharmacy Faculty Of Pharmaceutical Sciences Kyoto Pharmaceutical University
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Takara Kohji
Department Of Hospital Pharmacy School Of Medicine Kobe University
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Ohmoto Nobuko
Department Of Hospital Pharmacy School Of Medicine Kobe University
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Okamura N
Department Of Clinical Evaluation Of Pharmacotherapy Kobe University Graduate School Of Medicine
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Sakaeda Toshiyuki
Department Of Hospital Pharmacy Kobe University Hospital
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Hirai Midori
Department Of Applied Biology And Chemistry Faculty Of Applied Bio-science Tokyo University Of Agric
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Shirakawa T
Kobe University School Of Medicine
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IIDA Nami
Department of Hospital Pharmacy, School of Medicine, Kobe University
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Homma M
Department Of Pharmaceutical Sciences Graduate School Of Comprehensive Human Sciences University Of
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Horinouhi Masanori
Department Of Hospital Pharmacy School Of Medicine Kobe University
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Okumura Katsuhiko
Department Of Hospital Pharmacy School Of Medicine Kobe University
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Iida Nami
Department Of Hospital Pharmacy School Of Medicine Kobe University
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Okumura Katsuhiko
Department Of Clinical Evaluation Of Pharmacotherapy Kobe University Graduate School Of Medicine
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Okumura Katsuhiko
Department Of Hospital Pharmacy Kyoto Pharmaceutical University:department Of Hospital Pharmacy Kobe
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Nakamura Tsutomu
Department Of Gastroenterological Surgery Kobe University Graduate School Of Medical Sciences
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Nakamura Takeshi
Department Of Gastroenterological Surgery Kobe University Graduate School Of Medical Sciences
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Nakamura T
Department Of Hospital Pharmacy School Of Medicine Kobe University
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Sakai T
Department Of Internal Medicine And Gastrointestinal Endoscopy Saga Medical School
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Homma Masato
Department Of Pharmaceutical Sciences Graduate School Of Comprehensive Human Sciences University Of
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Koishi Tomokazu
Department Of Hospital Pharmacy Faculty Of Pharmaceutical Sciences Kyoto Pharmaceutical University
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Nakamura Tsutomu
Department Of Chemistry Nara Womens University
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Kimura Takashi
Department Of Medicine And Molecular Science Division Of Frontier Medical Science Programs For Biome
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Wada Atsushi
Department Of Cardiology Chigasaki Municipal Hospital
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Nakamura Tsutomu
Department Of Chemistry Faculty Of Science Faculty Of Agriculture Kyoto Unviersity
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Kimura Takashi
Department Of Comparative Pathology Faculty Of Veterinary Medicine Hokkaido University
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KIMURA Takashi
Department of Cardiovascular, Respiratory and Metabolic Medicine Graduate School of Medicine, Kagoshima University
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