Effects of Kampo Medicines on MDR-1-Mediated Multidrug Resistance in Human Hepatocellular Carcinoma HuH-7/PTX Cells
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概要
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Paclitaxel-resistant HuH-7 (HuH-7/PTX) cells were established by one-week exposure of HuH-7 cells to paclitaxel to analyze the effects of Kampo medicines on MDR-1-mediated multidrug resistance. HuH-7/PTX cells expressed high levels of MDR-1 and efficiently exported calcein-acetoxymethylester (calcein-AM), which is a substrate of MDR-1, suggesting that HuH-7/PTX cells resist paclitaxel by overexpressing MDR-1. We assessed the effects of 26 kinds of Kampo medicine on MDR-1 by calcein-AM efflux assay using HuH-7/PTX cells, and the results revealed that takushato and goreisan are potential inhibitors of drug efflux by MDR-1. Additionally, the sensitivity of HuH-7/PTX cells to paclitaxel was increased in combination with these Kampo medicines, indicating that takushato and goreisan overcame paclitaxel resistance in the cells by suppressing drug export by MDR-1. We further clarified that Alismatis Rhizoma contained in both takushato and goreisan reversed paclitaxel resistance by preventing drug efflux by MDR-1 without affecting the expression levels of MDR-1. Moreover, the principal components of Alismatis Rhizoma, Alisol A, Alisol B, and Alisol B acetate, were found to increase the sensitivity to paclitaxel in HuH-7/PTX by inhibiting drug export by MDR-1 without affecting the expression levels of MDR-1. These results suggested that the reversal effects of takushato and goreisan on paclitaxel resistance are derived from these principal components in Alismatis Rhizoma. Accordingly, Kampo medicines containing Alismatis Rhizoma such as takushato and goreisan may be useful as MDR-1 inhibitors.
- 公益社団法人 日本薬学会の論文
著者
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Hyuga Masashi
Division Of Biological Chemistry And Biologicals National Institute Of Health Sciences
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Hyuga Sumiko
Department Of Clinical Research Oriental Medicine Research Center Kitasato Institute
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Hanawa Toshihiko
Department Of Clinical Research Oriental Medicine Research Center The Kitasato Institute
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Hori Atsushi
Department of Oriental Medicine, Doctoral Program of Medical Science, Graduate School of Medical Science, Kitasato University
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Hyuga Sumiko
Department of Clinical Research, Oriental Medicine Research Center, Kitasato University
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Hori Atsushi
Department of Oriental Medicine, Graduate School of Medical Sciences, Kitasato University
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Shiraishi Masumi
Department of Clinical Research, Oriental Medicine Research Center, Kitasato University
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