RAPID STIMULATION OF RHODAMINE-123 EFFLUX FROM MULTIDRUG-RESISTANT KB CELLS BY PROGESTERONE
RAPID STIMULATION OF RHODAMINE-123 EFFLUX FROM MULTIDRUG-RESISTANT KB CELLS BY PROGESTERONE
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DOI：
10.1016/0006-2952(93)90331-p
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发表时间：
1993-11-02
影响因子：
5.8
通讯作者：
DANNIES, PS
中科院分区：
文献类型：
--
作者：
JANCIS, EM;CHEN, HX;DANNIES, PS
罗丹明123是一种线粒体染料，可被癌细胞长时间保留。在研究这种染料保留的原因时，我们发现10 μ M孕酮在15分钟内引起了从KB V20 C细胞中罗丹明123流出的快速刺激，KB V20 C细胞过度表达多药耐药泵。孕酮没有刺激KB细胞的外排，不过度表达的泵，维拉帕米阻断罗丹明123外排在孕酮的存在或不存在，表明罗丹明123从KB V20 C细胞的多药耐药泵。孕酮不可能通过增加泵活性来刺激罗丹明123的外排，原因有二：（1）孕酮抑制柔红霉素从KB V20 C细胞的外排，因此它不能刺激所有药物的外排;（2）孕酮抑制罗丹明123从L1210/VMDRC细胞的外排，而对Adr（R）MCF 7细胞几乎没有影响;都过度表达了多药耐药泵。在KB V20 C细胞的实验中，孕酮是测试的最活跃的类固醇。在10 μ M时，孕酮引起70倍的刺激，脱氧皮质酮，睾酮，普罗米孕酮和雌二醇约20倍，其他药物几乎没有或没有影响。孕酮可能通过非基因组机制减少罗丹明123的细胞内结合，使染料可进入多药耐药泵。
Rhodamine 123 is a mitochondrial dye that is retained for prolonged periods by carcinoma cells. While investigating causes of retention of this dye, we found that 10 muM progesterone caused a rapid stimulation of efflux of rhodamine 123 within 15 min from KB V20C cells, which overexpress the multidrug resistance pump. Progesterone did not stimulate efflux from KB cells that do not overexpress the pump, and verapamil blocked rhodamine 123 efflux in the presence or absence of progesterone, indicating that rhodamine 123 is removed from KB V20C cells by the multidrug resistance pump. Progesterone, however, is unlikely to stimulate rhodamine 123 efflux by simply increasing pump activity for two reasons: (1) progesterone inhibited the efflux of daunomycin from KB V20C cells, so it did not stimulate efflux of all drugs, and (2) progesterone inhibited efflux of rhodamine 123 from L1210/VMDRC cells and had little effect on Adr(R) MCF7 cells; both overexpress the multidrug resistance pump. In the experiments with KB V20C cells, progesterone was the most active steroid tested. At 10 muM, progesterone caused a 70-fold stimulation, desoxycorticosterone, testosterone, promegestone and estradiol about 20-fold, and others had little or no effect. Progesterone may act by a non-genomic mechanism to decrease intracellular binding of rhodamine 123, making the dye accessible to the multidrug resistance pump.