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中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志  2017, Vol. 37 Issue (3): 1-9    DOI: 10.13523/j.cb.20170301
研究报告     
EGF类生长因子来源的新型靶向肽在抗肿瘤药物蛋白中的应用
陈坤1, 曹雪玮1, 张琴2, 赵健1, 王富军2,3
1. 华东理工大学生物反应器工程重点实验室 上海 200237;
2. 浙江日升昌药业有限公司 东阳 322100;
3. 上海中医药大学中药研究所 上海 201203
Application of EGF-like Growth Factor-derived Tumor-homing Peptide for Antineoplastic Protein
CHEN Kun1, CAO Xue-wei1, ZHANG Qin2, ZHAO Jian1, WANG Fu-jun2,3
1. State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China;
2. Zhejiang Reachall Pharmaceutical Co. Ltd, Dongyang 322100, China;
3. Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
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摘要:

许多肿瘤细胞表面表皮生长因子受体EGFR都存在过表达现象。考察了牛痘病毒生长因子(VGF)中的EGFR结合域(S3)与人的肝素样表皮生长因子(HB-EGF)来源的肝素结合域(命名为HE)重组后对肿瘤细胞的选择性。通过重组表达带有靶向和穿膜结构域的EGFP-S3-HE和EGFP-S3-HE-TATm两种融合蛋白与正常细胞和肿瘤细胞的共孵育实验来研究其对肿瘤细胞的特异性靶向吸附和穿膜效应。进一步将S3-HE-TATm靶向穿膜序列与苦瓜来源的核糖体失活蛋白MAP30融合,可显著提高MAP30对肿瘤细胞的抑杀作用,但这种抑杀作用却对正常细胞仍保持在较低水平。由此表明S3-HE-TATm是一种新型优异的肿瘤细胞靶向药物运输载体,可用于肿瘤治疗的进一步开发研究。

关键词: 肿瘤靶向肽牛痘病毒生长因子细胞穿膜肽表皮生长因子抗肿瘤药物    
Abstract:

Many studies have showed epidermal growth factor receptors (EGFR) were overexpressed in various types of cancer cells. The S3, an EGFR-binding domain derived from vaccinia virus growth factor (VGF), when fused to HE, a heparin binding domain derived from heparin-binding epidermal growth factor (HB-EGF),could enhance its tumor-homing ability. The incubation experiment of the fusion protein EGFP-S3-HE/EGFP-S3-HE-TATm (TAT is cell penetrating peptide) with normal/tumor cells proved that both the recombinant proteins had tumor cell specific targeting ability and significant penetrating effect.The fusion of S3-HE-TATmwith MAP30, a ribosome inactivation protein derived from Momordica charantia, significantly increased the inhibitory effect of MAP30 to tumor cells but still remained relatively low level effect to normal cells, Therefore, S3-HE-TATm is a new type of drug delivery vector for tumor targeting treatment.

Key words: Tumor-homing peptide    Epidermal growth factor    Anti-tumor drug    VGF    Cell penetrating peptides
收稿日期: 2016-11-20 出版日期: 2017-03-25
ZTFLH:  Q71  
基金资助:

国家自然科学基金资助项目(81171449)

通讯作者: 赵健     E-mail: zhaojian@ecust.edu.cn
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引用本文:

陈坤, 曹雪玮, 张琴, 赵健, 王富军. EGF类生长因子来源的新型靶向肽在抗肿瘤药物蛋白中的应用[J]. 中国生物工程杂志, 2017, 37(3): 1-9.

CHEN Kun, CAO Xue-wei, ZHANG Qin, ZHAO Jian, WANG Fu-jun. Application of EGF-like Growth Factor-derived Tumor-homing Peptide for Antineoplastic Protein. China Biotechnology, 2017, 37(3): 1-9.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.20170301        https://manu60.magtech.com.cn/biotech/CN/Y2017/V37/I3/1

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