van der Graaf W T, Mulder N H, Meijer C, de Vries E G
Department of Internal Medicine, University Hospital, Groningen, The Netherlands.
Cancer Chemother Pharmacol. 1995;35(4):345-8. doi: 10.1007/BF00689457.
The cytotoxic action of two morpholino anthracyclines, methoxymorpholino anthracycline (MRA-MT, FCE 23,762) and cyanomorpholino anthracycline (MRA-CN), was compared with the cytotoxicity of doxorubicin (DOX), the topoisomerase II inhibitor etoposide (VP-16), the topoisomerase I inhibitor camptothecin, methotrexate, and cisplatin in GLC4, a human small-cell lung-cancer cell line, in GLC4-Adr, its P-glycoprotein (Pgp)-negative, multidrug-resistant (MDR; 100-fold DOX-resistant) subline with overexpression of the MDR-associated protein (MRP) and a lowered topoisomerase II activity, and in GLC4-CDDP, its cisplatin-resistant subline. GLC4-Adr was about 2-fold cross-resistant for the morpholino anthracyclines and GLC4-CDDP was, relative to GLC4, more resistant for the morpholino anthracyclines than for DOX. Overall, MRA-CN was about 2.5-fold more cytotoxic than MRA-MT. The cytotoxicity profile of the morpholino anthracyclines in these cell lines mimicked that of camptothecin.
将两种吗啉代蒽环类药物，即甲氧基吗啉代蒽环类药物（MRA-MT，FCE 23,762）和氰基吗啉代蒽环类药物（MRA-CN）的细胞毒性作用，与阿霉素（DOX）、拓扑异构酶II抑制剂依托泊苷（VP-16）、拓扑异构酶I抑制剂喜树碱、甲氨蝶呤和顺铂在人小细胞肺癌细胞系GLC4、其P-糖蛋白（Pgp）阴性、多药耐药（MDR；对DOX耐药100倍）且过表达多药耐药相关蛋白（MRP）并降低拓扑异构酶II活性的亚系GLC4-Adr以及其顺铂耐药亚系GLC4-CDDP中的细胞毒性进行了比较。GLC4-Adr对吗啉代蒽环类药物有大约2倍的交叉耐药性，并且相对于GLC4，GLC4-CDDP对吗啉代蒽环类药物的耐药性比对DOX的耐药性更强。总体而言，MRA-CN的细胞毒性比MRA-MT大约高2.5倍。吗啉代蒽环类药物在这些细胞系中的细胞毒性谱与喜树碱的相似。
