Jiang X R, Newland A C, Macey M G, Jenkins G C, Miki T, Adachi K, Yamabe S
Department of Hematology, Royal London Hospital, U.K.
J Chemother. 1992 Oct;4(5):306-11. doi: 10.1080/1120009x.1992.11739183.
The antitumor activity of novel doxorubicin analogues YM1, YM3, YM4 and YM6 was evaluated against drug sensitive U937 monocytic leukemia and CCRF-CEM lymphoid leukemia cell lines, as well as drug resistant CEM/VLB100 lymphoid multidrug resistant leukemia cell line by a [3H]thymidine incorporation assay. Different antileukemic activities of these new anthracyclines were observed in our studies. These novel anthracyclines produced a dose- and time-dependent inhibition in all the leukemic cell lines tested, while YM1 and YM3 were more effective than YM4 and YM6 against all the leukemic cell lines. The antitumor activity of all these novel analogues was lower than that of doxorubicin or epidoxorubicin in drug sensitive leukemic cells. The relative resistance values (IC50 of resistant cell line/IC50 of sensitive parental cell line) of YM1, 3, 4 and 6 were 27, 7, 5 and 14 respectively. These were lower than the resistance values for ADM and EDR which were 45 and 40 respectively. YM3 had a similar antileukemic activity against the CEM/VLB100 drug resistant leukemic cell line to ADM or EDR with a lower relative resistance value and a slightly increased IC50 value. Our results suggest that YM3 may be used in high dose for the clinical treatment of leukemias with possible less cardiotoxicity as well as less drug resistance.
通过[3H]胸苷掺入试验，评估了新型阿霉素类似物YM1、YM3、YM4和YM6对药物敏感的U937单核细胞白血病细胞系、CCRF - CEM淋巴细胞白血病细胞系以及耐药的CEM/VLB100淋巴细胞多药耐药白血病细胞系的抗肿瘤活性。在我们的研究中观察到了这些新型蒽环类药物不同的抗白血病活性。这些新型蒽环类药物在所有测试的白血病细胞系中均产生了剂量和时间依赖性抑制，而YM1和YM3在所有白血病细胞系中比YM4和YM6更有效。在药物敏感的白血病细胞中，所有这些新型类似物的抗肿瘤活性均低于阿霉素或表阿霉素。YM1、3、4和6的相对耐药值（耐药细胞系的IC50/敏感亲本细胞系的IC50）分别为27、7、5和14。这些低于阿霉素和表阿霉素的耐药值，分别为45和40。YM3对CEM/VLB100耐药白血病细胞系的抗白血病活性与阿霉素或表阿霉素相似，相对耐药值较低且IC50值略有增加。我们的结果表明，YM3可能用于白血病的高剂量临床治疗，可能具有较低的心脏毒性以及较少的耐药性。
