氮芥新衍生物抗白血病细胞活性研究

Study on Anti Leukemia Activity of New Nitrogen Mustard Derivatives

对合成的氮芥新衍生物(化合物Y-65)进行了白血病细胞的抗增殖活性研究。采用MTT法检测化合物Y-65对3种白血病细胞(慢性粒细胞白血病细胞(K562)、人急性白血病细胞(CCRF-CEM)、人早幼粒急性白血病细胞(HL-60))及人正常肝上皮细胞(L02)的抗增殖效果,并通过测定时间浓度依赖曲线、观察白血病细胞的形态、Hoechst33258染色、Annexin V-FITC和PI染色以及JC-1线粒体染色一系列实验,研究化合物Y-65诱导白血病细胞CCRF-CEM的初步凋亡机制。结果表明:化合物Y-65对3种白血病细胞(K562,CCRF-CEM,HL-60)均有较好抗增殖活性(IC_(50)分别为:25.9±1.7,4.3±0.3,12.4±6.2μmol/L),特别是对K562细胞的抗增殖活性明显高于苯丁酸氮芥(CLB)对K562细胞的抗增殖活性。研究其凋亡机制发现,经过化合物Y-65作用的CCRF-CEM细胞,可能是通过改变线粒体膜电位来诱导白血病细胞发生凋亡,且化合物Y-65诱导细胞凋亡呈现时间和浓度依赖。设计合成的氮芥新衍生物Y-65对白血病细胞有较强的抗增殖活性。

The antiproliferative activity of a synthetic nitrogen mustard derivative(compound Y-65)on leukemia cells was studied.The antiproliferation effects of the compound on three kinds of leukemia cells(chronic myeloid leukemia cells(K562),human acute leukemia cells(CCRF-CEM),human promyelocytic acute leukemia cells(HL-60))and human normal liver epithelial cells(L02)were detected by MTT method.Through a series of experiments like measuring the time concentration dependent curve and observing the morphology of leukemia cells,Hoechst33258 staining,Annexin V-FITC and PI staining,and JC-1 mitochondrial staining were used to study the preliminary apoptosis mechanism of compound Y-65 inducing leukemia cell CCRF-CEM.The results show that compound Y-65 has good antiproliferative activity against three kinds of leukemia cells(K562,CCRF-CEM and HL-60)(IC_(50):25.9±1.7,4.3±0.3,12.4±6.2μmol/L,respectively),especially its antiproliferative activity against K562 cells is significantly higher than that of Chlorambucil(CLB).Further study of its apoptosis mechanism found that CCRF-CEM cells treated with compound Y-65 may induce apoptosis of leukemia cells by changing mitochondrial membrane potential,and compound Y-65 inducing apoptosis is in time and concentration dependent manners.The new nitrogen mustard derivatives,compound Y-65,has strong antiproliferative activity on leukemia cells.