Antimetastatic Activity of Polymeric RGDT Peptides Conjugated with Poly(ethylene glycol)
Antimetastatic Activity of Polymeric RGDT Peptides Conjugated with Poly(ethylene glycol)
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与聚乙二醇缀合的聚合 RGDT 肽的抗转移活性
DOI：
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
I. Azuma
中科院分区：
文献类型：
--
作者：
I. Saiki;J. Yoneda;Y. Igarashi;M. Aoki;N. Kusunose;K. Ono;I. Azuma
含有确定的RGDT序列重复或环状结构的聚合物肽，（RGDT）n（n = 1至11）和环状（RGDT）n（n=2至4），在500 μg剂量下与肿瘤细胞共注射后对实验性肺转移表现出抑制作用，并且作用的程度随着RGDT序列重复程度的增加而平行增加。（RGDT）n（n = 1、5、11）与聚（乙二醇）、PEG作为聚合物载体的偶联导致肺转移抑制增强，与RGDT序列重复程度成比例，并呈剂量依赖性。在原发性肿瘤切除前2天和3天间隔多次静脉注射PEG-（RGDT）11，可有效抑制皮下自发性肺转移。（RGDT）11仅在以2天间隔给药时表现出对肺转移的抑制作用。这表明PEG与（RGDT）n的缀合允许给药间隔的延长，意味着对肿瘤转移的持续抑制作用。为了支持这一假设，当PEG-（RGDT）11与肿瘤细胞共同静脉注射或在肿瘤接种前一天静脉注射时，观察到肺中放射性标记肿瘤细胞的阻滞减少。相比之下，（RGDT）11仅在与肿瘤细胞共注射时显著抑制肺中的肿瘤细胞停滞。我们还注意到（RGDT）n、cyclo（RGDT）n和PEG-（RGDT）11以浓度依赖性方式抑制肿瘤细胞侵入Matrigel，并与RGDT序列重复程度成比例，表明肽介导的抗转移作用部分与抗侵袭潜力相关。因此，抗细胞粘附和抗转移RGDT肽与PEG的缀合可能为预防癌症转移（“抗粘附疗法”）提供治疗上有希望的基础。
Polymeric peptides containing defined repetitive or cyclic structures of RGDT sequence, (RGDT)n (n = 1 to 11) and cyclo(RGDT)n (n=2 to 4), at a dose of 500 μg exhibited an inhibitory effect on experimental lung metastasis upon co‐injection with tumor cells and the magnitude of the effect increased in parallel with the increase of degree of repetition of the RGDT sequence. The conjugation of (RGDT)n (n = 1, 5, 11) with poly(ethylene glycol), PEG as a polymeric carrier led to enhanced inhibition of lung metastasis in proportion to the degree of RGDT sequence repetition and in a dose‐dependent manner. Multiple i.v. administrations of PEG‐(RGDT)11, at 2‐day and 3‐day intervals before the excision of primary tumors, effectively inhibited spontaneous lung metastasis by s.c. inoculation of tumors, whereas (RGDT)11 exhibited inhibition of lung metastasis only when given at 2‐day intervals. This indicates that the conjugation of PEG with (RGDT)n allowed the prolongation of administration interval, implying a sustained inhibitory effect on tumor metastasis. In support of this supposition, a decrease in the arrest of radiolabeled tumor cells in the lungs was observed when PEG‐(RGDT)11 was co‐injected i.v. with tumor cells, or injected i.v. one day before tumor inoculation. In contrast, (RGDT)11 significantly inhibited the tumor cell arrest in the lungs only upon co‐injection with tumor cells. We also noted that (RGDT)n, cyclo(RGDT)n and PEG‐(RGDT)11 inhibited tumor cell invasion into Matrigel in a concentration‐dependent manner and in proportion to the degree of RGDT sequence repetition, indicating that the peptide‐mediated antimetastatic effect is partly associated with the anti‐invasive potential. Thus, the conjugation of anti‐cell adhesive and antimetastatic RGDT peptide with PEG might provide a therapeutically promising basis for the prevention of cancer metastasis (“anti adhesion therapy”).
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DOI：
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发表时间：
1983
期刊：
Symposium on Fundamental Cancer Research
影响因子：
--
作者：
Fidler,IJ
通讯作者：
Fidler,IJ
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影响因子：
11.2
作者：
Nicolson,GL
通讯作者：
Nicolson,GL
影响因子：
56.9
作者：
HUMPHRIES, MJ;OLDEN, K;YAMADA, KM
通讯作者：
YAMADA, KM
影响因子：
15.9
作者：
HUMPHRIES, MJ;YAMADA, KM;OLDEN, K
通讯作者：
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