Kaneda Y, Yamamoto S, Kihira T, Tsutsumi Y, Nakagawa S, Miyake M, Kawasaki K, Mayumi T
Faculty of Pharmaceutical Sciences, Osaka University, Suita, Japan.
Invasion Metastasis. 1995;15(3-4):156-62.
This study was conducted to determine the mechanisms for the enhanced inhibitory effect of cell-adhesive peptides conjugated to polyethylene glycol (PEG) on tumor metastasis. Tyr-Ile-Gly-Ser-Arg (YIGSR), a laminin-derived peptide, conjugated with amino-PEG (YIGSR-aPEG) inhibited lung metastasis of B16-BL6 melanoma cells more effectively than unconjugated YIGSR peptide. [125I]-YIGSR-aPEG and native [125I]-YIGSR showed similar biphasic elimination and profiles after intravenous injection into C57BL/6 mice. Both [125I]-YIGSR and [125I]-YIGSR-aPEG expressed similar plasma half-lives and organ distributions. The radioactivity of both compounds was transported rapidly from the blood to the kidneys, and immediately excreted into the urine. [125I]-YIGSR was almost completely degraded in the urine, but [125I]-YIGSR-aPEG was not. In an in vitro stability assay, [125I]-YIGSR was degraded immediately upon incubation with mouse serum, whereas [125I]-YIGSR-aPEG was not degraded after 180 min incubation in mouse serum. These findings indicate that the enhanced inhibitory effect of YIGSR-aPEG on lung metastasis might be due to its increased stability in the blood.
本研究旨在确定与聚乙二醇（PEG）偶联的细胞黏附肽对肿瘤转移增强抑制作用的机制。源自层粘连蛋白的肽Tyr-Ile-Gly-Ser-Arg（YIGSR）与氨基聚乙二醇偶联（YIGSR-aPEG）比未偶联的YIGSR肽更有效地抑制B16-BL6黑色素瘤细胞的肺转移。将[125I]-YIGSR-aPEG和天然[125I]-YIGSR静脉注射到C57BL/6小鼠体内后，显示出相似的双相消除和分布情况。[125I]-YIGSR和[125I]-YIGSR-aPEG的血浆半衰期和器官分布相似。两种化合物的放射性均迅速从血液转运至肾脏，并立即排泄到尿液中。[125I]-YIGSR在尿液中几乎完全降解，但[125I]-YIGSR-aPEG则不会。在体外稳定性试验中，[125I]-YIGSR与小鼠血清孵育后立即降解，而[125I]-YIGSR-aPEG在小鼠血清中孵育180分钟后未降解。这些发现表明，YIGSR-aPEG对肺转移增强的抑制作用可能归因于其在血液中稳定性的提高。
