Effects of verapamil on etoposide, vincristine, and adriamycin activity in normal human bone marrow granulocyte-macrophage progenitors and in human K562 leukemia cells in vitro.
Effects of verapamil on etoposide, vincristine, and adriamycin activity in normal human bone marrow granulocyte-macrophage progenitors and in human K562 leukemia cells in vitro.
复制标题
维拉帕米对体外正常人骨髓粒细胞-巨噬细胞祖细胞和人 K562 白血病细胞中依托泊苷、长春新碱和阿霉素活性的影响。
作者：
J. Yalowich;J. Zucali;M. Gross;W. Ross
我们研究了维拉帕米对人白血病K562细胞以及正常人骨髓粒细胞-巨噬细胞祖细胞（CFU-GM）中足叶乙甙、长春新碱和阿霉素细胞毒性的影响。足叶乙甙对K562细胞的作用是对正常人骨髓CFU-GM的10倍。同样，长春新碱对K562细胞的细胞毒性约为对人骨髓CFU-GM的10倍。与此相反，阿霉素表现出对K562细胞与正常骨髓CFU-GM在1小时的孵育期的实验很少的选择性。在维拉帕米（2.5-10 μ M）的存在下，依托泊苷的细胞毒性在恶性和正常细胞中均增强。维拉帕米增强了长春新碱（0.1 μ M）对K562细胞的细胞毒性，但对正常骨髓CFU-GM的毒性无增强作用。阿霉素，另一方面，没有显示任何钙拮抗剂介导的增强细胞毒性在恶性或正常组织。这些结果表明，短期（1小时）与依托泊苷，长春新碱，阿霉素孵育产生不同的毒性，无论是单独使用或与化学增敏剂，如钙拮抗剂。这些活性差异与这三类抗癌药物细胞内分布的不同机制一致，值得进一步研究，特别是与钙拮抗剂联合使用。
We have examined the effects of verapamil on the cytotoxicity of etoposide, vincristine, and Adriamycin in human leukemia K562 cells as well as in normal human bone marrow granulocyte-macrophage progenitors (CFU-GM). Etoposide was 10-fold more potent against K562 cells than against normal human bone marrow CFU-GM. Similarly, vincristine cytotoxicity was about 10-fold greater against K562 cells than against human bone marrow CFU-GM. In contrast, Adriamycin exhibited little selectivity for K562 cells versus normal bone marrow CFU-GM during the 1-h incubation period of the experiments. In the presence of verapamil (2.5-10 microM), etoposide cytotoxicity was enhanced in both malignant and normal cells. Verapamil enhanced vincristine (0.1 microM) cytotoxicity in K562 cells but did not potentiate Vinca alkaloid toxicity in normal bone marrow CFU-GM. Adriamycin, on the other hand, did not display any calcium antagonist-mediated potentiation of cytotoxicity in either malignant or normal tissue. These results indicate that short-term (1 h) incubations with etoposide, vincristine, and Adriamycin yield different profiles of toxicities whether used alone or with chemosensitizing agents such as the calcium antagonists. These differences in activities are consistent with different mechanisms for intracellular disposition of these three classes of anticancer agents and are worthy of further investigation, especially with regard to combinations with calcium antagonists.
大剂量依托泊苷的药代动力学。
影响因子：
6.7
作者：
Newman,EM;Doroshow,JH;Forman,SJ;Blume,KG
通讯作者：
Blume,KG