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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。
In this study, human breast cancer MCF-7 cells and human erythroleukemia K562 cells were used as test cells, respectively MTT colorimetric, flow cytometry, RT-PCR detection of luteinizing hormone releasing hormone peptide modified methotrexate methotrexate modified by luteinizing hormone-releasing hormone peptide (LH-RH-MTX) on cell proliferation and its effect on cell cycle, apoptosis and LHRHR mRNA expression. The results showed that the inhibitory effect of LH-RH-MTX on the proliferation of MCF-7 cells was significantly higher than that of K562 cells. The inhibitory effect of LH-RH-MTX on the proliferation of MCF-7 cells was significantly higher than that of free MTX. The inhibitory effect of nucleated cells was obviously less than that of free MTX. After treated with LH-RH-MTX, the number of S phase cells increased significantly, the apoptosis rate increased significantly, and the relative expression of LHRHR mRNA decreased significantly. LH-RH can be used as a guide molecule to deliver the drug to the highly expressed LHRHR tumor cells, reduce the side effects of drugs and improve the therapeutic index.