环九肽与人乳腺癌MDA-MB-231细胞特异性结合的研究  

Study on specific binding between cyclic peptide and MDA-MB-231 cells of human breast cancer

作　　者：谢彦[1] 刘璐[2] 张俊[2] 周欢[2] 吴清华[2] 钟英[2] 孙晋[2] 陈道桢[2] 王莹莹[1] 程光华[1] 

机构地区：[1]皖南医学院附属弋矶山医院核医学科 [2]东南大学附属中大医院核医学科

出　　处：《中国临床药理学与治疗学》2014年第6期615-619,共5页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家自然科学基金资助项目(81202032;81372480);无锡市医院管理中心联合科技攻关计划项目(YGZX1213)

摘　　要：目的:探讨99 Tcm标记分子探针与人乳腺癌MDA-MB-231细胞的特异结合及生物分布。方法:Western blot分析MDA-MB-231细胞和正常乳腺上皮细胞MCF-10AIL-11受体(IL-11R)蛋白的表达;荧光检测99 Tcm-DTPA-c(CGRRAGGSC)与乳腺癌细胞的特异性结合及结合位点。18只荷瘤裸鼠随机分为6组(n=3),经尾静脉注入0.74MBq(0.1mL)分子探针,不同时间测量其在荷瘤鼠体内生物分布。结果:Western blot检测MDA-MB-231细胞IL-11R是MCF-10A细胞的6.7倍;荧光染色证实99 TcmDTPA-c(CGRRAGGSC)-FITC特异结合在MDA-MB-231细胞的胞质和胞膜中;乳腺癌细胞IL-11R结合分子探针具饱和性;分子探针在荷瘤鼠体内迅速、持续聚集在瘤体内,4h达峰值(17.63±1.73)%ID/g,其他脏器分布极少,差异有统计学意义(P<0.05)。结论:MDA-MB-231细胞呈IL-11R高表达,与环九肽具有高亲和力,99 Tcm标记环九肽放射性分子探针体内外能与之靶向特异结合。AIM： To investigate the specific binding between 99Tcm radiomarked molecular probe and MDA-MB-231 cells of human breast cancer and biodistribution in mice in vivo. METHODS： The different expression of IL-11R in MDA-MB-231 tumor cells and normal mam- mary epithelial cells （MCF-10A） were examined by Western blot. The specific binding of 99 TcTM- DTPA-c （CGRRAGGSC）and binding site with MDA-MB-231 cells were observed by a fluorescence microscope. Eighteen tumor-bearing nude mice were randomly divided into 6 groups （n = 3）, biodistribution in vivo in the nude mice were observed in different times after intravenous injection 0.74 MBq （0.1 mL） of the molecular probe. RESULTS： The expression of IL-11R in MDA-MB-231 tumor cells group was 6.7 times as MCF-10A cells group. Fluorescent staining confirmed that 99 Tc^m-DTPA- c （CGRRAGGSC）-FITC was located in the cell membrane and cytoplasm of MDA-MB-231. The combination between molecular probe ang IL-11R in MDA-MB- 231 cells possessed saturability. The radioactive molecular probe was rapidly, continually concentrated in the tumor tissue of the mice, and peaked （17.63＋1.73）% ID/g 4 h later. But the radioactive molecular probe was not obviously observed in other vital organs （P〈0.05）. CON- CLUSION. The IL-11R is highly expressed in MDA-MB-231 cells and has high affinity with the cyclic peptide. The 99Tcm labelled cyclic peptide, which is the radioactive molecular probe, has the specific targeted binding ability with MDA-MB-231 cells in vivo and in vitro.

关 键 词：环九肽 肿瘤 乳腺癌 MDA-MB-231 

分 类 号：R965.2[医药卫生—药理学]