INHIBITION OF TUMOR-METASTASIS BY A SYNTHETIC-POLYMER CONTAINING A CELL-ADHESIVE RGDS PEPTIDE
INHIBITION OF TUMOR-METASTASIS BY A SYNTHETIC-POLYMER CONTAINING A CELL-ADHESIVE RGDS PEPTIDE
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DOI：
10.1177/088391159300800305
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发表时间：
1993-07-01
影响因子：
1.7
通讯作者：
ITOH, I
中科院分区：
文献类型：
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作者：
KOMAZAWA, H;SAIKI, I;ITOH, I
合成了含有细胞粘附Arg-Gly-Asp-Ser (RGDS)序列的水溶性聚合物，即聚(羧乙基甲基丙烯酰胺-RGDS)缀合物[聚(CEMA-RGDS)]。 Poly(CEMA-RGDS) 以剂量依赖性方式（20-1000 微克）抑制 B16-BL6 黑色素瘤细胞的肺转移和 L5178Y-ML25 淋巴瘤细胞的肝转移。聚(CEMA)和RGDS肽的混合物或单独的聚(CEMA)对肺转移没有表现出任何抑制作用。 Gly-Arg-Gly-Asp-Ser (GRGDS) 肽需要高剂量（3000 杯）才能获得足够的抗转移效果。体外研究表明，聚 (CEMA-RGDS) 以及 RGDS + 聚 (CEMA) 对 B16-BL6 细胞侵入重建基底膜基质胶的抑制作用相似。间歇性四．与多次施用RGDS、聚(CEMA)或未处理的对照相比，接种B16-BL6细胞后施用聚(CEMA-RGDS)引起自发性肺转移的显着抑制。这些结果表明，RGDS肽与聚合物载体的缀合增加了对癌症转移的治疗潜力，这意味着RGDS-聚合物缀合可能导致RGDS肽在体内的抗转移作用延长。
A water soluble polymer containing cell adhesive Arg-Gly-Asp-Ser (RGDS) sequence, i.e., poly(carboxyethylmethacrylamide-RGDS) conjugate [poly(CEMA-RGDS)], was synthesized. Poly(CEMA-RGDS) inhibited lung metastasis of B16-BL6 melanoma cells in a dose-dependent manner (20-1000 mug) and liver metastasis of L5178Y-ML25 lymphoma cells. A mixture of poly(CEMA) and RGDS peptide or poly(CEMA) alone did not show any inhibitory effect on lung metastasis. The Gly-Arg-Gly-Asp-Ser (GRGDS) peptide required high doses (3000 mug) to obtain a sufficient antimetastatic effect. An in vitro study showed that poly(CEMA-RGDS) as well as RGDS + poly(CEMA) gave similar inhibition of B16-BL6 cell invasion into reconstituted basement membrane Matrigel. Intermittent iv. administration of poly(CEMA-RGDS) after inoculation with B16-BL6 cells caused significant inhibition of spontaneous lung metastasis as compared with the multiple administration of RGDS, poly(CEMA) or untreated control. These results demonstrate that the conjugation of RGDS peptide with a polymeric carrier increases therapeutic potential to cancer metastasis, implying that RGDS-polymer conjugation may lead to the prolongation of antimetastatic action of RGDS peptide in vivo.