ジヒドロピリジン誘導体による多剤耐性の克服 Overcoming drug resistance in cancer cells with dihydropyridine analogues ジヒドロピリジン ユウドウタイ ニヨル タザイ タイセイ ノ コクフク
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Bibliographic Information
- Title
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ジヒドロピリジン誘導体による多剤耐性の克服
- Other Title
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Overcoming drug resistance in cancer cells with dihydropyridine analogues
- Other Title
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ジヒドロピリジン ユウドウタイ ニヨル タザイ タイセイ ノ コクフク
- Author
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神渡, 幹夫
- Author(Another name)
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カンド, ミキオ
- University
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鹿児島大学
- Types of degree
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医学博士
- Grant ID
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乙第861号
- Degree year
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1990-04-25
Note and Description
博士論文
Ten synthetic dihydropyridine analogues were investigated for their ability to reverse drug-resistance in a multidrug-resistant human carcinoma cell line, KB-Cl. Four dihydropyridine analogues completely reversed the resistance, 3 lowered the resistance and 3 had little effect. The radioactive photoactive dihydropyridine calcium channel blocker, [^3H] azidopine, photolabels P-glycoprotein in membrane vesicles from KB-Cl cells. This photolabeling was almost completely inhibited by excess dihydropyridine analogues that reversed or lowered drug-resistance. In contrast, the labeling was not significantly inhibited by analogues that do not reverse resistance. Among other reversing agents, cepharanthine and reserpine inhibited the [^3H] azidopine photolabeling, but thioridazine did not. SDB-ethylenediamine slightly inhibited the labeling at 100μM. An anticancer agent, vinblastine also inhibited the labeling. The correlation between the reversing of the drug-resistance and the inhibition of the [^3H] azidopin photolabeling of P-glycoprotein by dihydropyridine analogues suggests a role for P-glycoprotein in multidrug-resist ance and also the reversing of the resistance by dihydropyridine analogues.
医歯学総合研究科博士論文(医学) ; 学位取得日: 平成2年4月25日