叶酸偶联5-氟尿嘧啶-白蛋白对肿瘤细胞的毒性及靶向性研究  

Study on the cytotoxicity and targeting ability of folate-conjugated 5-fluorouracil-albumin on tumor cells

作　　者：张武雄[1] 凌丽[1] 何练芹[1] 臧林泉[1] 潘雪刁[1] 朱亮[1] 

机构地区：[1]广东药学院药科学院,广东广州510006

出　　处：《广东药学院学报》2009年第4期405-408,共4页Academic Journal of Guangdong College of Pharmacy

摘　　要：目的研究叶酸偶联5-氟尿嘧啶-白蛋白在体外对肿瘤细胞的毒性及经叶酸受体介导的靶向性。方法选用叶酸受体表达阳性FR(+)宫颈癌HeLa细胞及叶酸受体表达阴性FR(-)肺癌A549细胞进行实验。用MTT法观察叶酸偶联物对细胞的毒性作用,同时利用游离叶酸能与叶酸偶联物竞争性结合叶酸受体的原理,考察叶酸偶联物是否具有经叶酸受体介导的靶向性。结果叶酸偶联物对FR(+)HeLa细胞具有比5-氟尿嘧啶原料药更高的抑制率,能有效的靶向FR(+)HeLa细胞,且细胞毒性作用能被过量的外源性游离叶酸所抑制,而叶酸偶联物对FR(-)A549细胞作用很弱。结论叶酸偶联的5-氟尿嘧啶-白蛋白能经叶酸受体介导靶向于叶酸受体丰富的肿瘤细胞。Objective To study the cytotoxicity and targeting ability of folate-conjugated 5-fluorouracilalbumin via folate receptor-mediated endocytosis on tumor cells in vitro. Methods The folate receptor positive FR（ ＋ ） HeLa cell and FR（-） lung A549 cell were used for experiment. The cytotoxicity of the folate-conjugate on tumor cells was measured by MTT assay. According to the competitive inhibition principle and due to that free folate had high affinity for folate receptor, free folic acid was used to validate whether folate-conjugate has the targeting ability to FR （ ＋ ） HeLa cell via folate receptor-mediated endocytosis. Results The cytotoxicity of folate-eonjugate to FR （ ＋ ） HeLa cell was stronger than 5- fluorouracil crude drug in the same concentration, and could be inhibited by excess free folic acid, while the cytotoxicity on FR （ - ） lung A549 cell was very weak. Conclusion Folate-conjugated 5-fluorouracilalbumin could be targeted into tumor cells with rich folate receptors via folate receptor-mediated endocytosis significantly.

关 键 词：叶酸偶联 5-氟尿嘧啶 细胞毒性 靶向性 

分 类 号：R73-36[医药卫生—肿瘤]