Novel EGFR-targeted strategy with hybrid peptide against oesophageal squamous cell carcinoma.
Novel EGFR-targeted strategy with hybrid peptide against oesophageal squamous cell carcinoma.
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DOI：
10.1038/srep22452
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发表时间：
2016-03-09
影响因子：
4.6
通讯作者：
Kawakami K
中科院分区：
文献类型：
--
作者：
Kikuchi O;Ohashi S;Horibe T;Kohno M;Nakai Y;Miyamoto S;Chiba T;Muto M;Kawakami K
表皮生长因子受体（EGFR）是食管鳞状细胞癌（OSCC）病理生理过程中的关键分子。然而，用于OSCC的egfr靶向药物，如抗egfr抗体或酪氨酸激酶抑制剂，尚未显示出任何临床益处。最近，一种新的化疗药物，EGFR(2R)-裂解混合肽，一种EGFR结合肽和裂解肽片段的复合物，已被证明对表达高EGFR水平的癌症表现出有效的抗肿瘤作用。在这项研究中，我们研究了体外和体内使用EGFR（2R）裂解杂交肽对OSCC细胞的有效性。此外，在小鼠中评估了该肽的毒性。我们发现在OSCC细胞的细胞表面有高水平的EGFR表达，并且EGFR结合肽片段对OSCC细胞表现出高亲和力。暴露于EGFR(2R)-裂解杂化肽的OSCC细胞在30分钟内诱导了强大的细胞毒性作用。此外，在异种移植模型中，EGFR（2R）裂解杂化肽显著抑制OSCC细胞的肿瘤生长。此外，它在小鼠身上没有引起任何可识别的不良反应。综上所述，EGFR(2R)-裂解杂化肽被证明是一种有效的OSCC治疗剂，为新的EGFR靶向OSCC治疗提供了重要的理论依据。
Epidermal growth factor receptor (EGFR) is a key molecule in the pathophysiology of oesophageal squamous cell carcinoma (OSCC). However, EGFR-targeted agents such as anti-EGFR antibody or tyrosine kinase inhibitors for OSCC have not demonstrated any clinical benefits. Recently, a novel chemotherapeutic agent, EGFR(2R)-lytic hybrid peptide, a composite of EGFR-binding peptide and lytic peptide fragments, has been shown to exhibit a potent anti-tumour effect against cancers that express high EGFR levels. In this study, we investigated the validity of employing EGFR(2R)-lytic hybrid peptide against OSCC cells both in vitro and in vivo. Additionally, the toxicity of this peptide was assessed in mice. We found high EGFR expression levels on the cell surface of OSCC cells, and the EGFR-binding peptide fragment showed high affinity for OSCC cells. A potent cytotoxic effect was induced within 30 minutes by the exposure of OSCC cells to EGFR(2R)-lytic hybrid peptide. Furthermore, EGFR(2R)-lytic hybrid peptide markedly suppressed the tumour growth of OSCC cells in a xenograft model. Moreover, it did not cause any identifiable adverse effects in mice. Taken together, EGFR(2R)-lytic hybrid peptide was shown to be a valid therapeutic agent against OSCC, providing a crucial rationale regarding novel EGFR-targeted therapies against OSCC.