津白Ⅱ小鼠体内筛选乳腺癌特异性结合噬菌体融合肽  

Selection of phage and characterization of peptides specific binding to breast cancer in vivo

作　　者：王瑞[1] 张霖[1] 张宏恺[2] 魏熙胤[1] 杨毅[1] 李萌辉[1] 曹又佳[2] 牛瑞芳[1] 

机构地区：[1]天津医科大学肿瘤医院中心实验室,乳腺癌防治教育部重点实验室,天津300060 [2]南开大学

出　　处：《天津医科大学学报》2008年第2期138-141,共4页Journal of Tianjin Medical University

基　　金："863"国家高技术研究发展计划(2006AA02Z19C)

摘　　要：目的:利用噬菌体随机肽库,筛选特异性靶向乳腺癌的肽段,为乳腺癌的定位诊断和靶向治疗提供理论依据。方法:建立津白Ⅱ(TAⅡ)小鼠自发乳腺癌模型,并在小鼠体内对噬菌体十二随机肽库进行4轮筛选,回收肿瘤和对照组织(肝)的噬菌体并计数,同时用免疫组织化学染色法,鉴定噬菌体展示肽的特异性。结果:筛选出自发乳腺癌特异性结合的噬菌体,其结合乳腺癌细胞的能力为对照组织的14倍,随机挑选克隆测序鉴定,结果表明十二肽ASANPF-PTKALL出现次数最多,免疫组化染色进一步证明该噬菌体能特异结合于乳腺癌细胞。结论:4次小鼠体内筛选得到的短肽ASANPFPTKALL能够特异结合于乳腺癌组织,为下一步的定位诊断和靶向治疗研究奠定了基础。Objective： To screen from a phage-displayed peptide library polypeptide fragments specific binding to breast cancer xenografts in vivo, and provide for anti-tumor treatment. Methods： Mice models for breast cancer xenografts were established by Tientsin Albinao Ⅱmice （TA Ⅱ ）. The 12-peptide library was panned through 4 rounds. Phages were recovered and titrated from tumor xenografts and control tissue （liver）. The distribution of phage were detected by immunohistochemical staining. Results： Phage homing to breast cancer were enriched through four rounds of panning, being 14 fold of that recovered from liver tissue. Peptide sequences were characterized for randomly picked-up clones and the peptide sequence ASANPFPTKALL appeared most frequently. Immunohistochemical staining revealed a specific breast cell localization in cancer xenografts 40 mins after injection of the enriched phages. When the specific phage individually tested,the phage recovered from breast cancer xenografts were as 14 times as those from control tissue. Conclusion： The tumor-specific homing peptides ASANPFPTKALL may provide a effective tool for targeting breast cell in therapy of cancer. In vivo phage display selection technique in this study is feasible and applicable to screening peptides homing to breast cells.

关 键 词：噬菌体展示 乳腺癌细胞 体内筛选 小鼠 

分 类 号：R383.24[医药卫生—医学寄生虫学] R737.9[医药卫生—基础医学]