Design and biological activity of epidermal growth factor receptor-targeted peptide doxorubicin conjugate
Design and biological activity of epidermal growth factor receptor-targeted peptide doxorubicin conjugate
复制标题
表皮生长因子受体靶向肽阿霉素缀合物的设计和生物活性
DOI：
10.1016/j.biopha.2015.01.027
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发表时间：
2015-03-01
影响因子：
7.5
通讯作者：
Shi, Bizhi
中科院分区：
文献类型：
--
作者：
Fan, Mingliang;Yang, Danbo;Shi, Bizhi
抗癌药物阿霉素（DOX）对肿瘤细胞和正常细胞的非特异性毒性会导致严重的副作用，从而限制了其临床应用。在本工作中，表皮生长因子受体（EGFR）拮抗剂肽GE 11通过二硫键引入DOX结构中，该二硫键可被还原型谷胱甘肽（GSH）切割。我们研究了GE 11-DOX缀合物和游离DOX在高（SMMC-7721）和低（MCF-7）EGFR表达癌细胞模型中的细胞内递送和体外细胞毒性。GE 11-DOX在SMMC-7721细胞中的蓄积水平高于MCF-7细胞，而细胞对游离DOX的摄取在两种细胞中几乎相同。此外，用抗EGFR单克隆抗体预处理减少SMMC-7721中GE 11-DOX的细胞内积聚，表明EGFR途径参与缀合物的转运。我们的研究结果表明，GE 11-DOX偶联物具有成为治疗EGFR过表达肿瘤的治疗剂的潜力。(C)2015年Elsevier Masson SAS。All rights reserved.
The nonspecific toxicity of anticancer drug doxorubicin (DOX) toward both tumor and normal cells can result in serious side effects, thereby limiting its clinical applications. In this wok, epidermal growth factor receptor (EGFR) antagonist peptide GE11 was introduced into DOX structure via a disulfide bond which can be cleaved by reduced glutathione (GSH). We have investigated the intracellular delivery and in vitro cytotoxicity of GE11-DOX conjugate and free DOX in high (SMMC-7721) and low (MCF-7) EGFR expressing cancer cell models. GE11-DOX accumulated at higher levels in SMMC-7721 cells than in MCF-7 cells, while the cellular uptake of free DOX was almost the same in both cells. Furthermore, pretreating with anti-EGFR monoclonal antibody reduced intracellular accumulation of GE11-DOX in SMMC-7721, indicating the involvement of EGFR pathway in the transport of conjugate. Our results suggest that GE11-DOX conjugate has the potential to be a therapeutic agent for treating EGFR overexpressing tumor. (C) 2015 Elsevier Masson SAS. All rights reserved.