Flow cytometric monitoring of anthracycline transport in tumor cells.
Flow cytometric monitoring of anthracycline transport in tumor cells.
复制标题
流式细胞仪监测肿瘤细胞中蒽环类药物的转运。
DOI：
10.1111/j.1749-6632.1986.tb42030.x
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发表时间：
1986
影响因子：
5.2
通讯作者：
Krishan,A
中科院分区：
文献类型：
--
作者：
Krishan,A
蒽环类药物如阿霉素和道诺霉素是重要的癌症化疗药物。各种蒽环类药物在细胞运输和结合特性上的主要差异已经被描述。&“大多数蒽环类化合物是荧光的，可以很容易地用氩激光器发射的488nm激光激发。”一些众所周知的蒽环类药物，如阿霉素，是通过细胞膜缓慢转运的，而另一些（如道诺霉素）是快速转运的。阿霉素和道诺霉素与染色质结合，而蒽环类药物如ad32不与染色质结合。大多数蒽环类药物具有高荧光性，因此非常适合通过激光激发和流式细胞术进行分析。这种技术提供了基于细胞荧光识别亚群的优势。对药物摄取的快速监测，以及可以通过其他方法对选定的细胞进行分类以进行进一步分析的附加优势。在早期的报道中，我们已经使用这种方法来监测组织培养细胞、耐药细胞和注射阿霉素的动物分离组织中蒽环类药物的转运。4.~细胞对蒽环类药物的耐药已被认为是由于耐药细胞的药物快速外排机制。因此，影响药物外排和增强药物保留的药物可以改变细胞对蒽环类药物的耐药性。最近的几项研究表明，实际上钙通道阻滞剂和吩噻嗪会抑制耐药细胞的药物外排，从而使它们对药物敏感。如果在使用蒽环类药物和影响其细胞外排的药物之前，我们可以在体外筛选肿瘤细胞的蒽环类药物转运特性，这将是有用的。如下章节所示，我们使用激光流式细胞术（用于激发细胞内蒽环类药物含量）监测肿瘤细胞中的药物荧光，并监测药物外排阻断剂对药物滞留的影响。
Anthracyclines such as adriamycin and daunomycin are important cancer chemotherapeutic agents.'Major differences in cellular transport and binding characteristics of various anthracyclines have been described. &'Most of the anthracyclines are fluorescent and can be easily excited with the 488 nm laser emission from an argon laser.". 5 Some of the well-known anthracyclines such as adriamycin are slowly transported across cellular membranes while others (eg, daunomycin) are rapidly transported?.'Whereas adriamycin and daunomycin bind to chromatin: anthracyclines such as AD 32 do not bind to chromatin.'Most of the anthracylines are highly fluorescent and thus are ideally suited for analysis by laser excitation and flow cytometry. This technique offers the advantage of identifying subpopulations based on their cellular fl~ orescence?~ rapid monitoring of drug uptake and the added advantage that selected cells can be sorted for further analysis by other means. In earlier reports we have used this method for monitoring anthracycline transport in tissue culture cells, in drug resistant cells, and in tissues isolated from animals injected with adriamy~ in. 4.~Cellular resistance to anthracyclines has been suggested to be due to a mechanism for rapid drug efflux from resistant cells? Thus, drugs that will affect drug efflux and enhance drug retention can modify cellular resistance to anthracyclines. Several recent studies have shown that in fact calcium channel blockers and phenothiazines will inhibit drug efflux from resistant cells and thereby render them drug sensitive. 1-16 It would be useful if before the administration of anthracyclines and agents that affect their cellular efflux in vivo, we could screen tumor cells in vitro for their anthracycline transport characteristics. As shown in the following sections, we have used laser flow cytometry (for excitation of intracellular anthracycline content) to monitor drug fluorescence in tumor cells and to monitor the effect of drug efflux blocking agents on drug retention.