肽修饰的甲氨蝶呤体外抗肿瘤作用初步研究  

In vitro anti-tumor effect of methotrexate modified by peptide

作　　者：周雅梅[1] 吴学萍[1] 曾理[1] 张雅溶[1] 潘黎军[1] 王驰[1] 

机构地区：[1]重庆医科大学药学院,重庆400016

出　　处：《药学学报》2012年第4期452-458,共7页Acta Pharmaceutica Sinica

基　　金：重庆市渝中区科技计划项目(20100205)

摘　　要：本文以人乳腺癌MCF-7细胞及人红白血病K562细胞作为受试细胞,分别采用MTT比色法、流式细胞仪、RT-PCR技术检测促黄体激素释放激素肽修饰的甲氨蝶呤(methotrexate modified by luteinizing hormone-releasing hormone peptide,LH-RH-MTX)对细胞增殖的抑制作用以及对细胞周期和凋亡、LHRHR mRNA表达量的影响。结果显示,LH-RH-MTX对MCF-7细胞增殖的抑制作用明显高于K562细胞;相同浓度的LH-RH-MTX对MCF-7细胞增殖的抑制作用明显高于游离MTX,对鼠骨髓单核细胞的抑制作用明显小于游离MTX;经LH-RH-MTX作用后,S期细胞明显增加,细胞凋亡率明显升高,LHRHR mRNA的相对表达量明显下降。LH-RH可作为导向分子将药物靶向递送到LHRHR高表达的肿瘤细胞,降低药物的毒副作用,提高治疗指数。This study is to investigate the anti-tumor effect in vitro of methotrexate modified by LH-RH peptide （LH-RH-MTX）. LH-RH receptors highly expressing MCF-7 human breast carcinoma cell line and lowly expressing K562 human erythroleukemia cell line were served as the tested cells. The cell proliferation inhibition rates of LH-RH-MTX were detected by MTT colorimetric assay. The effects of LH-RH-MTX on the cell cycle and apoptosis rates were detected by flow cytometry. The inhibition rate of LH-RH-MTX on MCF-7 cells was much higher than that on K562 cells, and the inhibition rate of LH-RH-MTX on MCF-7 cells was much higher than that of free MTX at the same concentration. The inhibition rate of LH-RH-MTX on rat bone marrow mononuclear cells was less than that of free MTX. The number of MCF-7 cells in S phase increased after administration of LH-RH-MTX. The apoptosis rate of LH-RH-MTX group significantly increased compared with that of the control group and MTX group. The relative expression of LHRHR mRNA of LH-RH-MTX group markedly decreased compared with that of the control group and MTX group. LH-RH- MTX is realizable to reduce drug side effects, increase the therapeutic index and achieve tumor-targeted therapy.

关 键 词：甲氨蝶呤 促黄体激素释放激素 LH-RH-MTX 靶向药物传递系统 抗肿瘤作用 

分 类 号：R965[医药卫生—药理学] R979.1[医药卫生—药学]