Antitumor effect of RGD-4C-GG-D(KLAKLAK)2 peptide in mouse B16(F10) melanoma model
Antitumor effect of RGD-4C-GG-D(KLAKLAK)2 peptide in mouse B16(F10) melanoma model
复制标题
DOI：
10.18388/abp.2006_3309
复制
发表时间：
2006-01-01
影响因子：
1.7
通讯作者：
Szala, Stanislaw
中科院分区：
文献类型：
--
作者：
Smolarczyk, Ryszard;Cichon, Tomasz;Szala, Stanislaw
在过去的几年中，血管靶向剂已经被测试为癌症治疗剂。这样的治疗可以使用例如双功能（双结构域）肽来完成。RGD 4C-GG-（D）（KLAKLAK）（2）是Ellerby及其同事（1999）设计的一种肽（全序列：ACDCRGDCFCGGKLAKLAKKLAKLAK），选择性结合肿瘤新生血管系统中表达的α（V）α（3）整联蛋白受体，内化后有效诱导内皮细胞凋亡。本研究的目的是检查RGD-4C-GG-（D）（KLAKLAK）（2）是否能有效靶向过表达α（V）β（3）受体的细胞（其中包括B16（F10）），以及它是否适用于原发性B16（F10）小鼠黑色素瘤的治疗。因此，肽将靶向两个不同的肿瘤区室：由血管内皮形成的区室和由肿瘤细胞组成的区室。在B16（F10）细胞系中，治疗肽被识别并诱导凋亡。直接瘤内给药后观察到肿瘤生长抑制。然而，肽施用的停止导致动物的快速肿瘤生长和死亡。
Vasculature targeting agents have been tested as cancer therapeutics for the past few years. Such therapy could be accomplished using, for example, bifunctional (two-domain) peptides. RGD4C-GG-(D) (KLAKLAK)(2), a peptide designed by Ellerby and coworkers (1999) (full sequence: ACDCRGDCFCGGKLAKLAKKLAKLAK), binds selectively to alpha(V)alpha(3) integrin receptors expressed in tumor neovasculature and, after internalization, effectively induces apoptosis of endothelial cells. The aim of this study was to examine if RGD-4C-GG-(D)(KLAKLAK)(2) would efficiently target cells, among them B16(F10), that overexpress alpha(V)beta(3) receptors, and whether it would be suitable for therapeutic treatment of primary B16(F10) murine melanoma tumors. Thus, the peptide would target two distinct tumor compartments: that formed by endothelium of blood vessels and that made up of neoplastic cells. The therapeutic peptide was recognized and did induce apoptosis in B16(F10) cell line. Tumor growth inhibition was observed following direct intratumoral administration. However, cessation of peptide administration led to rapid tumor growth and death of the animals.