逆转 ABC 药物转运蛋白介导的肿瘤细胞多药耐药：现有策略的评估。
Reversal of ABC drug transporter-mediated multidrug resistance in cancer cells: evaluation of current strategies.
机构信息
Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
出版信息
Curr Mol Pharmacol. 2008 Jun;1(2):93-105. doi: 10.2174/1874467210801020093.
Abstract
Overexpression of ATP-binding cassette (ABC) drug transporters that actively efflux a variety of amphipathic compounds can cause multidrug resistance (MDR) in cancer cells, which is a major obstacle in the success of cancer chemotherapy. The development of synthetic small molecule compounds or the identification of natural products that block ABC transporter-mediated efflux has been the conventional approach used to combat MDR. The strategy of using chemosensitizers, however, has not been successful in clinical cancer chemotherapy. Therefore, alternative approaches to identify or to synthesize compounds that can induce selective toxicity in cancer cells overexpressing one or more ABC transporters have been undertaken. This review summarizes the recent advances in identifying strategies to restore sensitivity to chemotherapeutics in multidrug resistant cancer cells.
摘要
三磷酸腺苷结合盒（ABC）药物转运蛋白的过度表达可使多种两亲性化合物主动外排，从而导致癌细胞的多药耐药（MDR），这是癌症化疗成功的主要障碍。合成小分子化合物或鉴定天然产物以阻断 ABC 转运蛋白介导的外排一直是用于对抗 MDR 的常规方法。然而，使用化学增敏剂的策略在临床癌症化疗中并未取得成功。因此，已经采取了替代方法来鉴定或合成可在过度表达一种或多种 ABC 转运蛋白的癌细胞中诱导选择性毒性的化合物。本文综述了近年来在鉴定使多药耐药癌细胞对化疗药物重新敏感的策略方面的进展。
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