Davey R A, Su G M, Hargrave R M, Harvie R M, Baguley B C, Davey M W
Bill Walsh Cancer Research Laboratories, Clinical Oncology Department, Royal North Shore Hospital, St. Leonards, Australia.
Cancer Chemother Pharmacol. 1997;39(5):424-30. doi: 10.1007/s002800050593.
The effectiveness of N-[2-(dimethylamino)ethyl]acridine-4-carboxamide (DACA) relative to that of amsacrine, idarubicin, daunorubicin and paclitaxel against three different forms of multidrug resistance (MDR) was determined using two sublines of the CCRF-CEM human leukaemia cell line, the P-glyco-protein-expressing CEM/VLB100 subline and the MRP-expressing CEM/E1000 subline, and two extended-MDR sublines of the HL60 human leukaemia cell line, HL60/E8 and HL60/V8. DACA was effective against P-glycoprotein-mediated MDR and MRP-mediated MDR, whereas the extended-MDR phenotype showed only low levels of resistance (< 2-fold) to DACA. In comparison, idarubicin was ineffective against the MRP and extended-MDR phenotypes. Repeated exposure of the K562 human leukaemia cell line to DACA (55, 546 or 1092 nM for 3 days over 10 weeks) did not result in the development of any significant drug resistance. We conclude that DACA has the potential to treat refractory leukaemia.
使用CCRF-CEM人白血病细胞系的两个亚系，即表达P-糖蛋白的CEM/VLB100亚系和表达多药耐药相关蛋白（MRP）的CEM/E1000亚系，以及HL60人白血病细胞系的两个扩展多药耐药（extended-MDR）亚系HL60/E8和HL60/V8，确定了N-[2-(二甲氨基)乙基]吖啶-4-甲酰胺（DACA）相对于安吖啶、伊达比星、柔红霉素和紫杉醇对三种不同形式多药耐药（MDR）的有效性。DACA对P-糖蛋白介导的MDR和MRP介导的MDR有效，而扩展MDR表型对DACA仅表现出低水平耐药（<2倍）。相比之下，伊达比星对MRP和扩展MDR表型无效。将K562人白血病细胞系反复暴露于DACA（55、546或1092 nM，在10周内分3天处理）未导致产生任何显著的耐药性。我们得出结论，DACA有治疗难治性白血病的潜力。
