本文選題：肽庫 + 前列腺癌��； 參考：《腫瘤防治研究》2017年09期

【摘要】：目的利用細菌鞭毛肽庫技術(shù)篩選與高轉(zhuǎn)移潛能的前列腺癌PC-3M-1E8細胞特異結(jié)合的多肽片段。方法利用細菌鞭毛肽庫對人前列腺癌高低轉(zhuǎn)移配對細胞株P(guān)C-3M-1E8和PC-3M-2B4進行篩選,獲得與前列腺癌高轉(zhuǎn)移細胞親和的細菌克隆。將結(jié)合能力最強細菌克隆所共同擁有的重復(fù)多肽序列挑選出來并化學合成;利用熒光染色和流式細胞儀,通過細胞親和、競爭拮抗實驗及荷瘤小鼠模型,鑒定合成肽與前列腺癌高轉(zhuǎn)移細胞的體內(nèi)外的結(jié)合特異性。結(jié)果篩選出一段核心序列為NVVRQ的五肽,命名為TMTP1;FITC-TMTP1可特異地與PC-3M-1E8高度親和,且這種結(jié)合是濃度依賴并能為游離的TMTP1所拮抗;熒光顯微鏡檢測小鼠腫瘤及正常組織器官冰凍切片顯示FITC-TMTP1在腫瘤原發(fā)灶及轉(zhuǎn)移灶的熒光信號強度也要顯著強于正常組織器官。結(jié)論篩選獲得的短肽TMTP1可以特異地與高轉(zhuǎn)移潛能的前列腺癌細胞結(jié)合,為前列腺癌的靶向診療提供一種可能的標志物及靶向載體。
[Abstract]:Objective to screen polypeptide fragments specifically bound to prostate cancer PC-3M-1E8 cells with high metastatic potential by bacterial flagellin library technique. Methods Human prostate cancer cell lines PC-3M-1E8 and PC-3M-2B4 were screened by bacterial flagellin library, and bacterial clones with high affinity to prostate cancer cells were obtained. The repeated polypeptide sequences shared by bacterial clones with the strongest binding ability were selected and chemically synthesized. By means of cell affinity, competitive antagonism and tumor-bearing mouse models, fluorescence staining and flow cytometry were used. To identify the binding specificity of synthetic peptides to prostate cancer cells with high metastasis in vitro and in vivo. Results A pentapeptide with a core sequence of NVVRQ was selected and named TMTP1FITC-TMTP1, which was highly compatible with PC-3M-1E8, and the binding was concentration-dependent and antagonized by free TMTP1. Fluorescence microscopy showed that the fluorescence intensity of FITC-TMTP1 in primary tumor and metastatic tumor was significantly higher than that in normal tissue and organ. Conclusion the short peptide TMTP1 can specifically bind to prostate cancer cells with high metastatic potential and provide a possible marker and target vector for the diagnosis and treatment of prostate cancer.
【作者單位】： 華中科技大學同濟醫(yī)學院附屬同濟醫(yī)院婦產(chǎn)科;
【基金】：國家自然科學基金(81202061,81572563)
【分類號】：R737.25
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本文編號：1907319