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目的进一步探讨米托蒽醌抗癌作用机制，为临床联合用药提供理论指导。方法以小鼠艾氏腹水癌细胞破碎液为材料，通过ＤＥ－５２和Ｐ－１１层析柱，提取ＤＮＡ引物酶－多聚酶α复合体，研究米托蒽醌对ＤＮＡ引物酶－多聚酶α复合体活性的影响以及对引物合成和引物延长活性的作用。结果检测ＤＮＡ引物酶－多聚酶α复合体的比活性为６．０１３３×１０６Ｕｇ－１。米托蒽醌抑制ＤＮＡ引物酶－多聚酶α复合体活性的ＩＣ５０值为（１３．５４±０．８９）μｍｏｌＬ－１，随着药物浓度的增加，对ＤＮＡ引物酶－多聚酶α复合体活性的抑制作用增强。进一步研究米托蒽醌对引物合成或延长影响时发现，其对引物合成几乎无作用，可见是对ＤＮＡ引物酶－多聚酶α复合体的延长活性起抑制作用。结论米托蒽醌对ＤＮＡ复制的影响至少部分是因抑制ＤＮＡ引物酶－多聚酶α复合体的引物延长活性。
Objective To further explore the anti-cancer mechanism of mitoxantrone and provide theoretical guidance for clinical combination therapy. Methods The DNA-enzyme-polymerase-α complex was extracted from DE-52 and P-11 chromatographic columns using Ehrlich’s ascites tumor cell lysate as a material to study the effect of mitoxantrone on DNA-polymerase- Activity and its effect on primer synthesis and primer extension activity. Results The specific activity of the DNA polymerase-α complex was 6.0133 × 106Ug-1. Mitoxantrone inhibited the activity of DNAsease-polymerase alpha complex with an IC50 value of (13.54 ± 0.89) μmol L-1. With the increase of drug concentration, the activity of DNAsease-polymerase α complex was inhibited Enhance the role. Further study of mitoxantrone on the primer synthesis or extension of the effect found that it had little effect on the primer synthesis, it is seen on the DNA polymerase activity of the enzyme - polymerase alpha play a role in prolonging. Conclusion The effect of mitoxantrone on DNA replication is at least partly due to the inhibition of the primer extension activity of the DNA-polymerase-α complex.