Binding capability of the enediyne-associated apoprotein to human tumors and constitution of a ligand oligopeptide-integrated protein
Binding capability of the enediyne-associated apoprotein to human tumors and constitution of a ligand oligopeptide-integrated protein
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DOI：
10.1016/j.jbiotec.2009.09.001
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发表时间：
2009-10-26
影响因子：
4.1
通讯作者：
Zhen, Yongsu
中科院分区：
文献类型：
--
作者：
Cai, Lin;Chen, Hongxia;Zhen, Yongsu
力达霉素属于抗肿瘤抗生素的色蛋白家族，其分子由脱辅基蛋白（LDP）和烯二炔发色团组成。该分子的烯二炔部分负责有效的细胞毒性;然而，脱辅基蛋白部分的生物学功能，特别是其与癌细胞的相互作用，仍然不清楚。本研究首次利用组织芯片技术检测了LDP与人肿瘤细胞的结合能力。LDP与多种肿瘤的结合与相应的正常组织有显著差异。肺癌组织芯片证实VEGF和EGFR的过表达与结合活性呈正相关。通过DNA重组技术构建了LDP与EGFR配体寡肽的融合蛋白LG-LDP。LG-LDP表现出增强的EGFR过表达癌细胞的结合。此外，通过将活性烯二炔（AE）整合到LG-LDP分子中，制备了能量化融合蛋白LG-LDP-AE。MTT法显示LG-LDP-AE对肿瘤细胞具有极强的细胞毒作用，IC_（50）约为0.01 nM。结果表明，LDP可与多种人类肿瘤结合，并可作为递送载体，通过整合配体寡肽来制备基于模体的、针对癌症的融合蛋白。(C)2009爱思唯尔有限公司版权所有。
The molecule of lidamycin that belongs to the chromoprotein family of antitumor antibiotics is composed of an apoprotein (LDP) and an enediyne chromophore. The enediyne moiety of the molecule is responsible for the potent cytotoxicity; however, the biological function of the apoprotein moiety, particularly its interaction with cancer cells, remains unclear. In present study, the binding capability of LDP to human tumors was detected for the first time by tissue microarray. LDP bound to various human tumors with significant difference from the corresponding normal tissues. Positive correlation between binding activity and the overexpression of VEGF and EGFR was confirmed by lung carcinoma tissue microarray. A fusion protein LG-LDP that consists of LDP and a ligand oligopeptide to EGFR was constructed by DNA recombination. LG-LDP showed augmented binding to EGFR-overexpressing cancer cells. Furthermore, an energized fusion protein LG-LDP-AE was prepared by integrating the active enediyne (AE) into LG-LDP molecule. By MTT assay, LG-LDP-AE displayed extremely potent cytotoxicity to cancer cells with IC50 approximate to 0.01 nM. The results indicate that LDP binds to various human tumors and it might serve as a delivery carrier by integration of ligand oligopeptide to manufacture motif-based, targeted fusion proteins for cancer. (C) 2009 Elsevier B.V. All rights reserved.