Utz I, Gekeler V, Ise W, Beck J, Spitaler M, Grunicke H, Hofmann J
Institute of Medical Chemistry and Biochemistry, University of Innsbruck, Austria.
Anticancer Res. 1996 Jan-Feb;16(1):289-96.
We investigated whether the expression of protein kinase C (PKC) isoenzymes, topoisomerase II alpha, II beta, multidrug resistance associated protein (MRP), p53 or the activity of glutathione-S- transferase (GST) are additional factors contributing to the resistance mediated by multidrug resistance gene 1 (mdr 1). the cell lines employed for these studies were human lymphoblastoid CCRF cells selected for resistance with actinomycin D, vincristine and adriamycin, KB-3-1 and matched resistant KB-8-5 and KB-C1 cells (selected with colchicine), and a HeLa cell line, in which the resistance was obtained by transfection with the mdr1-gene. Analysis of PKC isozymes showed that there is no correlation of a specific isoenzyme with resistance, although minor differences in the expression were observed. In vincristine and adriamycin selected cells, topoisomerase II alpha- and II beta-MRNA levels were reduced, and in vincristine selected cells the MRP-mRNA was elevated compared with the sensitive line. In KB cells the levels of topoisomerase II alpha and II beta mRNA were increasing with the resistance. Expression of p53 did not correlate with Pgp levels. In summary, MRP and topoisomerase II may contribute to the mdr1 -mediated resistance in some cell lines, but PKC, p53 and GST seem to be of minor or no importance.
我们研究了蛋白激酶C（PKC）同工酶、拓扑异构酶IIα、IIβ、多药耐药相关蛋白（MRP）、p53的表达或谷胱甘肽-S-转移酶（GST）的活性是否是导致多药耐药基因1（mdr1）介导的耐药性的其他因素。用于这些研究的细胞系包括用人放线菌素D、长春新碱和阿霉素筛选出的耐药性人淋巴母细胞CCRF细胞、KB-3-1以及配对的耐药性KB-8-5和KB-C1细胞（用秋水仙碱筛选），还有通过转染mdr1基因获得耐药性的HeLa细胞系。PKC同工酶分析表明，尽管观察到表达存在微小差异，但特定同工酶与耐药性之间没有相关性。在长春新碱和阿霉素筛选的细胞中，拓扑异构酶IIα和IIβ的mRNA水平降低，而在长春新碱筛选的细胞中，与敏感细胞系相比，MRP的mRNA升高。在KB细胞中，拓扑异构酶IIα和IIβ的mRNA水平随着耐药性增加。p53的表达与P糖蛋白水平无关。总之，MRP和拓扑异构酶II可能在某些细胞系中导致mdr1介导的耐药性，但PKC、p53和GST似乎作用较小或无关紧要。
