偶联物5-氟尿嘧啶-花生凝集素对体外细胞毒作用的特性
In vitro characteristics of cytotoxic effect of 5-fluorouracil-peanut agglutinin conjugate
采用一步法制备得到花生凝集素-5-氟尿嘧啶偶联物，并进行了电泳性质研究。交联反应前，采用了EDC/NHS先活化药物和加D-半乳糖保护的方式。药物随后与PNA上的游离氨基发生反应生成酰胺键得到偶联物。利用垂直板SDS-PAGE电泳对偶联物的电泳行为和分子量进行了考察，以确定药物和载体的偶连方式。采用Lowry法测定蛋白含量，采用TNBS法测定药物结合率，采用胸腺细胞凝集实验法测定偶联物活性。应用MTT法,以靶细胞LoVo细胞和非靶细胞Chang细胞为细胞模型，检测偶联物的细胞毒作用特性。非活性偶联物和游离凝集素对靶细胞几乎不产生细胞毒作用，活性偶联物对靶细胞有明显抑制作用；活性偶联物对非靶细胞无细胞毒作用，游离药物对靶细胞和非靶细胞均有相似的细胞毒作用。说明活性偶联物的细胞毒作用具有明显的特异性和选择性。
Peanut agglutinin (PNA)was coupled by fixing its amino groups to the carbodiimide-activated carboxylic groups of 5-fluorouracil (5-Fu) derivative (N1-substituted 5-Fu acetate) N1to form 5-Fu-PNA conjugate one-step method. The property of the conjugate was detected on SDS-PAGE. The characteristics of cytotoxic effect of 5-Fu-PNA were examined on the human colorectal cancer cell line LoVo and the human normal liver cell line Chang using MTT assay. Compared with free drug, the active conjugate had similar cytotoxic effect on LoVo cells with much lower cytotoxicity on Chang cells. On the other hand, lower cytotoxic effects on LoVo cells were observed for non-active conjugate even at higher drug concentrations. The results indicated the specificity and selectivity of the cytotoxic effect of 5-Fu-PNA in vitro.
蔡勤、张志荣
药学基础医学肿瘤学
花生凝集素5-氟尿嘧啶偶联物细胞毒作用
Peanut agglutinin 5-fluorouracil conjugate cytotoxic effects
蔡勤,张志荣.偶联物5-氟尿嘧啶-花生凝集素对体外细胞毒作用的特性[EB/OL].(2009-03-06)[2025-08-16].http://www.paper.edu.cn/releasepaper/content/200903-195.点此复制
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