叶酸受体阳性肿瘤细胞对Folate-PGA偶联酶的特异性结合  

Specific binding of folate conjugated PGA to FR-positive tumor cells

作　　者：张奇[1] 张友九[2] 杨科亚[2] 项光亚[1] 

机构地区：[1]华中科技大学同济医学院药学院,湖北武汉430030 [2]苏州大学放射医学与公共卫生学院,江苏苏州215007

出　　处：《中国药理学通报》2007年第6期746-750,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No30300430)

摘　　要：目的考察叶酸受体阳性肿瘤细胞对叶酸偶联的青霉素G酰化酶(Folate-PGA)的特异性结合。方法采用Iodo-gen法标记的125I-Folate-PGA测定叶酸受体表达阳性FR(+)HeLa与SKOV3细胞以及叶酸受体表达阴性FR(-)A549细胞于4℃对Folate-PGA偶联酶的结合。结果125I-Folate-PGA对FR(-)A549无特异性结合;与HeLa和SK-OV3细胞的特异性结合的Kd分别为0.11nmol·L-1和0.25nmol·L-1。结论叶酸偶联的PGA酶对FR(+)肿瘤细胞具有较好的亲和力和靶向性,可用于叶酸导向的酶前体药物疗法的进一步研究。Aim To investigate the specific binding of folate conjugated PGA to FR-positive tumor cells.Method Folate-PGA and PGA were radiolabeled with ^125I by the Iodogen method to examine the binding of PGA to FR positive HeLa cells and SKOV3 cells, or FR negative A549 cells. Results ^125I-folate-PGA showed specific bound to HeLa cells and SKOV3 cells; Scatchard analysis of the data estimated the Kd of binding to be 0.11 nmol·L^-1 and 0.25 nmol·L^-1 respectively. ^125I-folate-PGA showed virtually little specific binding to A549 cells which lack folate receptors.Conclusions folate-PGA displayed high affinity and good targeting activities for FR-positive tumor cells and the data warranted further studies for enzyme prodrug therapy.

关 键 词：叶酸靶向 特异性结合 青霉素G酰化酶 偶联 

分 类 号：R329.24[医药卫生—人体解剖和组织胚胎学] R392.11[医药卫生—基础医学]