Cytotoxic Effects of 27 Anticancer Drugs in HeLa and MDR1-Overexpressing Derivative Cell Lines
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概要
- 論文の詳細を見る
The cytotoxic effects of 27 anticancer drugs including amrubicin, vinorelbine, paclitaxel, docetaxel, gemcitabine, and irinotecan were evaluated in human cervical carcinoma HeLa cells, and drug-resistant HeLa-derived Hvr1-1, Hvr10-6, and Hvr100-6 cells, which were newly established by stepwise exposure to viablastine. FACS and RT-PCR analysis indicated that MDR1 (P-glycoprotein) was induced without any alterations in expression of its related transporters. Hvr100-6 cells showed 2- to 200-fold higher resistance to anthracyclines than HeLa cells, and unexpectedly showed slight resistance to idarubicin and amrubicin. The relative resistance to vinca-alkaloids was 300- to 600000-fold, and Hvr100-6 cells showed the highest relative resistance to vinorelbine. Hvr100-6 cells also showed 4000- and 60000-fold resistance to the taxanes paclitaxel and docetaxel, respectively. Hvr100-6 cells were also resistant to 6-mercaptopurine, actinomycin D, etoposide, and mitomycin C, with relative resistance of 8-, 45000-, 12-, and 9-fold, respectively. In contrast, Hvr100-6 cells showed no or slight resistance to platinum derivatives, pyrimidine analogues, and alkylating agents or to irinotecan and its active form, or tamoxifen. The cytotoxicity of anthracyclines, vinca-alkaloids, taxanes, actinomycin D, and etoposide was extensively reversed by cyclosporin A. Cyclosporin A had no effect on the cytotoxicity of 6-mercaptopurine or mitomycin C, suggesting that resistance to these drugs was not mediated via MDR1. The alterations in cytotoxicity by overexpression of MDR1 and effects of cyclosporin A could be also qualitatively explained by I uptake experiments. The 27 anticancer drugs analyzed here could be classified into substrates and nonsubstrates for MDR1. This will be useful for designing effective regimens for chemotherapy.
- 社団法人日本薬学会の論文
- 2002-06-01
著者
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Nakamura T
Department Of Gastroenterological Surgery Kobe University Graduate School Of Medical Sciences
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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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Kobayashi H
Shionogi Research Laboratories Shionogi & Co. Ltd.
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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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Kobayashi Hironao
Shionogi Research Laboratories, Shionogi & Co., Ltd.,
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Nishiguchi Kohshi
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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YAGAMI Tatsurou
Shionogi Research Laboratories, Shionogi & Co., Ltd.
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HORINOUCHI Masanori
Department of Hospital Pharmacy, School of Medicine, Kobe University
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Okumura K
Department Of Clinical Evaluation Of Pharmacotherapy Kobe University Graduate School Of Medicine
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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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Shirakawa T
Kobe University School Of Medicine
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Yagami Tatsurou
2shionogi Research Laboratories Shionogi & Co. Ltd.
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Homma M
Department Of Pharmaceutical Sciences Graduate School Of Comprehensive Human Sciences University Of
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Yokoyama T
Kitasato Univ. Sagamihara Jpn
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Yokoyama T
Kyoto Pharmaceutical Univ. Kyoto Jpn
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Nishiguchi K
Department Of Hospital Pharmacy Kobe University School Of Medicine
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Nishiguchi Kohshi
Department Of Clinical Pharmacy Faculty Of Pharmaceutical Sciences Kyoto Pharmaceutical University
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Nishiguchi Kohshi
Department Of Hospital Pharmacy School Of Medicine Kobe University
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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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Kobayashi Hironao
Shionogi Research Laboratories Shionogi & Co. Ltd.
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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 Takeshi
Department Of Gastroenterological Surgery Kobe University Graduate School Of Medical Sciences
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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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Nagahiro Kazumi
Department Of Hospital Pharmacy Kobe University School Of Medicine
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Koishi Tomokazu
Department Of Hospital Pharmacy Faculty Of Pharmaceutical Sciences Kyoto Pharmaceutical University
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Yagami Tatsurou
Shionogi Research Laboratories Shionogi & Co. Ltd.
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