Ethacrynic acid and piriprost as enhancers of cytotoxicity in drug resistant and sensitive cell lines.
Ethacrynic acid and piriprost as enhancers of cytotoxicity in drug resistant and sensitive cell lines.
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发表时间：
1988-07
期刊：
影响因子：
11.2
通讯作者：
K. Tew;Annette M. Bomber;S. Hoffman
中科院分区：
文献类型：
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作者：
K. Tew;Annette M. Bomber;S. Hoffman
乙酸和匹利前列素（6,9-深氧-6,9-（苯基氨基）- δ 6,8-前列腺素11）已被证明能增强氯霉素对大鼠和人肿瘤细胞系的细胞毒活性。对氮芥（WR）获得性耐药的Walker 256大鼠乳腺癌细胞（WS）和2个人结肠癌细胞系HT 29和BE，在乙酸或匹利前列素作为烷基化剂同时给药时，对氯霉素致敏。以1-氯-2,4-二硝基苯为底物，对谷胱甘肽s -转移酶活性均有抑制作用。细胞内谷胱甘肽的耗竭在单独使用乙酸或与氯霉素联合使用后也很明显。因此，利尿植物酚或前列腺素类似物与烷基化剂联合使用可能具有潜在的治疗效用。
Ethacrynic acid and piriprost (6,9-deepoxy-6,9-(phenylimino)-delta 6,8-prostaglandin I1) have been shown to potentiate the cytotoxic activity of chlorambucil in rat and human tumor cell lines. Walker 256 rat breast carcinoma cells (WS), with acquired resistance to nitrogen mustards (WR), and two human colon carcinoma cell lines, HT 29 and BE, were sensitized to chlorambucil when either ethacrynic acid or piriprost was administered at the same time as the alkylating agent. Both as single agents and in combination with chlorambucil, there was inhibition of glutathione S-transferase activity as measured with 1-chloro-2,4-dinitrobenzene as a substrate. A depletion in intracellular glutathione was also evident following ethacrynic acid alone or in combination with chlorambucil. Thus, diuretic plant phenols or prostaglandin analogues may have potential therapeutic utility in combination with alkylating agents.