新型环孢菌素A类似物及体外生物合成的环缩肽SDZ 214-103对多药耐药性的逆转作用
Reversal of multidrug resistance by novel cyclosporin A analogues and the cyclopeptolide SDZ 214-103 biosynthesized in vitro.
作者信息
Schwabe K, Steinheider G, Lawen A, Traber R, Hildebrandt A
机构信息
Bundesinstitut für Arzneimittel und Medizinprodukte, Berlin, Federal Republic of Germany.
出版信息
J Cancer Res Clin Oncol. 1995;121(7):407-12. doi: 10.1007/BF01212947.
It was shown that cyclopeptolide SDZ 214-103 (10 microM) is more active in rhodamine-123 accumulation in actinomycin-D-resistant human lymphoma cells CCRF/ACTD400 than cyclosporin A (10 microM), but equipotent in the doxorubicin-resistant Friend erythroleukemia cell line F4-6/ADR. In F4-6/ADR cells, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assay showed comparable cytotoxic effects of doxorubicin at various concentrations in the presence of SDZ 214-103 and cyclosporin A. For the other novel cyclosporin A analogues minor multidrug-resistance-modulating potency was demonstrated. At equipotent modulating doses of verapamil (10 microM) and cyclosporin A (10 microM) in the MTT assay regarding doxorubicin cytotoxicity, cyclosporin A was efficient in the rhodamine-123-uptake assay while verapamil was not active when identical incubation times were used.
结果表明，环肽SDZ 214 - 103（10微摩尔）在放线菌素-D耐药的人淋巴瘤细胞CCRF/ACTD400中对罗丹明-123积累的活性比环孢素A（10微摩尔）更高，但在多柔比星耐药的Friend红白血病细胞系F4 - 6/ADR中活性相当。在F4 - 6/ADR细胞中，3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四氮唑溴盐（MTT）细胞毒性试验表明，在SDZ 214 - 103和环孢素A存在的情况下，不同浓度的多柔比星具有相当的细胞毒性作用。对于其他新型环孢素A类似物，显示出轻微的多药耐药调节效力。在MTT试验中，关于多柔比星细胞毒性，维拉帕米（10微摩尔）和环孢素A（10微摩尔）的等效调节剂量下，当使用相同的孵育时间时，环孢素A在罗丹明-123摄取试验中有效，而维拉帕米无活性。
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