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目的 从噬菌体肽库筛选TNF α相关短肽 ,为临床上治疗肿瘤奠定基础。方法 用可溶性TNF受体Ⅰ (sTNFRⅠ )筛选噬菌体随机 12肽库 ,利用细胞毒效应进行生物学效应筛选 ,再进行单链DNA测序。结果 分别得到若干模拟跨膜型TNF α(TM TNF α)和模拟分泌型TNF α(S TNF α)细胞毒效应的短肽 ,选择细胞毒效应最好的模拟TM TNF α短肽进行人工合成 ,体外实验显示此肽段对S TNF α耐受肿瘤细胞系HL 6 0具有明显细胞毒效应 ,且主要引起靶细胞凋亡。另外 ,利用激光共聚焦显微镜证实该合成肽段不能诱导NF κB发生核转位。结论 获得模拟TM TNF α的短肽 ,为TM TNF α用于临床抗瘤治疗提供新线索。
Objective To screen TNFα-related short peptides from phage peptide library and lay the foundation for the clinical treatment of tumors. Methods The phage random 12 - peptide library was screened by soluble TNF receptor Ⅰ (sTNFR Ⅰ). The cytotoxic effect was used to screen the biological effect and single - stranded DNA was sequenced. Results A number of short peptides, which mimic the cytotoxic effects of transmembrane TNFα (TM TNFα) and secreted TNFα (S TNFα), were obtained. The artificial TM TNFα short peptides with the best cytotoxic effect were selected and synthesized. In vitro experiments showed that this peptide has obvious cytotoxic effect on S TNFαtolerance tumor cell line HL 6 0, and mainly caused apoptosis of target cells. In addition, confocal laser scanning microscopy confirmed that the synthetic peptide failed to induce NF-κB nuclear translocation. Conclusion Obtaining short peptides that simulate TM TNFα provide new clues for the clinical use of TM TNFα in clinical anti-tumor therapy.