Destruction of breast cancers and their metastases by lytic peptide conjugates in vitro and in vivo
Destruction of breast cancers and their metastases by lytic peptide conjugates in vitro and in vivo
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DOI：
10.1016/j.mce.2005.12.056
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发表时间：
2007-01-02
影响因子：
4.1
通讯作者：
Leuschner, Carola
中科院分区：
文献类型：
--
作者：
Hansel, William;Enright, Fred;Leuschner, Carola
在一系列体内和体外实验中，已经确立了表达LH/CG或LHRH受体的乳腺癌细胞可以被由裂解肽片段和CG -链的15个氨基酸片段组成的构建物或LHRH裂解肽偶联物靶向和破坏的概念。体外获得的数据证实了这一概念的有效性，表明了hecate - β CG、Phor14和phor21 - β CG偶联物在杀死表达功能性LH/CG受体的细胞中的特异性，并证明了LH/CG受体容量与化合物的特异性直接相关。在体内实验中，hecate - β CG、phor14 - β CG和phor21 - β CG（ala）均能显著降低移植乳腺癌裸鼠的肿瘤体积和肿瘤负荷；单独使用Hecate和Phor21或与非特异性肽结合均无效。最重要的是，这些裂解肽偶联物在靶向和摧毁淋巴结、骨骼、肺部和其他器官的弥散性乳腺癌转移瘤方面都非常有效。2006爱思唯尔爱尔兰有限公司版权所有。
In a series of in vivo and in vitro experiments, the concept has been established that breast cancer cells that express LH/CG or LHRH receptors can be targeted and destroyed by constructs consisting of a lytic peptide moiety and a 15-amino acid segment of the beta-chain of CG or by an LHRH lytic peptide conjugate. Data obtained in vitro established the validity of this concept, showed the specificities of the Hecate-beta CG, and Phor14 and Phor21-beta CG conjugates in killing cells that express functional LH/CG receptors and proved that the LH/CG receptor capacity is directly related to the compound's specificity. In in vivo experiments, Hecate-beta CG, Phor14-beta CG, and Phor21-beta CG(ala) each caused highly significant reductions of tumor volurne and tumor burden in nude mice bearing breast cancer xenografts; Hecate and Phor21 alone or conjugated with non-specific peptides were not effective. Most importantly, the lytic peptide conjugates were all highly effective in targeting and destroying disseminated breast cancer metastases in lymph nodes, bones, lungs and other organs. (c) 2006 Elsevier Ireland Ltd. All rights reserved.