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首页> 外文期刊>Life sciences >Liposomes modified with a synthetic Arg-Gly-Asp mimetic inhibit lung metastasis of B16BL6 melanoma cells
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Liposomes modified with a synthetic Arg-Gly-Asp mimetic inhibit lung metastasis of B16BL6 melanoma cells

机译：用合成的Arg-Gly-Asp模拟物修饰的脂质体抑制B16BL6黑色素瘤细胞的肺转移

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摘要

Administration of large amounts of synthetic peptides based on the Arg-Gly-Asp (RGD) sequence has been shown to suppress tumor metastasis. To overcome the rapid degradation of peptides in the circulation, an RGD mimetic, L-arginyl-6-aminohexanoic acid (NOK), was synthesized and conjugated with phosphatidylethanolamine (PE) (NOK-PE) for liposomalization. Cell adhesion assays revealed that B16BL6 murine melanoma cells adhered to immobilized NOK-PE. This adhesion was inhibited by addition of either soluble RGDS or NOK at similar concentration in a dose-dependent manner. Administration of NOK-PE liposomes (equivalent to ca. 500 mug RGD peptides) via the tail vein completely inhibited lung colonization of B16BL6 cells. The same dose of soluble NOK was not effective in inhibition of the tumor metastasis. In addition, injection of NOK-PE liposomes via the tail vein inhibited spontaneous lung metastasis of B16BL6 cells from the primary tumor site in the hind footpad. These results suggest that NOK, a structural mimetic of RGD, is capable of suppressing metastasis by blockade of the binding of the integrins present on tumor cells to the RGD-containing extracellular matrix. (C) 2000 Elsevier Science Inc. All rights reserved. [References: 28]
机译：已显示基于Arg-Gly-Asp（RGD）序列的大量合成肽给药可抑制肿瘤转移。为了克服肽在循环中的快速降解，合成了RGD模拟物L-精氨酸-6-氨基己酸（NOK），并与磷脂酰乙醇胺（PE）（NOK-PE）偶联用于脂质体化。细胞粘附试验表明，B16BL6鼠黑色素瘤细胞粘附于固定的NOK-PE。通过以剂量依赖性方式添加相似浓度的可溶性RGDS或NOK可以抑制这种粘附。通过尾静脉施用NOK-PE脂质体（相当于约500杯RGD肽）完全抑制了B16BL6细胞的肺部定植。相同剂量的可溶性NOK不能有效抑制肿瘤转移。此外，通过尾静脉注射NOK-PE脂质体可抑制B16BL6细胞自后足垫原发肿瘤部位的自发肺转移。这些结果表明，NOK（一种RGD的结构模拟物）能够通过阻断肿瘤细胞上存在的整联蛋白与含RGD的细胞外基质的结合而抑制转移。 （C）2000 Elsevier Science Inc.保留所有权利。 [参考：28]

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