A single treatment with microcapsules containing a CXCR4 antagonist suppresses pulmonary metastasis of murine melanoma

被引:92
作者
Takenaga, M [1 ]
Tamamura, H
Hiramatsu, K
Nakamura, N
Yamaguchi, Y
Kitagawa, A
Kawai, S
Nakashima, H
Fujii, N
Igarashi, R
机构
[1] St Marianna Univ, Sch Med, Inst Med Sci, Kawasaki, Kanagawa 2168512, Japan
[2] Kyoto Univ, Grad Sch Pharmaceut Sci, Sakyo Ku, Kyoto 6068501, Japan
[3] St Marianna Univ, Sch Med, Dept Microbiol, Kawasaki, Kanagawa 2168511, Japan
关键词
B16-BL6; CXCR4; antagonist; melanoma; metastasis; poly D; L-lactic acids; sustained release;
D O I
10.1016/j.bbrc.2004.05.155
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Biodegradable Poly D,L-lactic acid (PLA, molecular weight: ca. 5000) microcapsules containing a CXCR4 antagonist (4F-benzoyl-TE14011) were prepared (4F-benzoyl-TE14011-PLA), and their anti-metastatic activity was evaluated in mice. A single subcutaneous administration of 4F-benzoyi-TE14011-PLA significantly reduced the number of colonies formed by pulmonary metastasis of B16-BL6 melanoma cells expressing CXCR4. The same dose of 4F-benzoyl-TE14011 in a single or a series of treatments affected little. The substance 4F-benzoyl-TE14011 dose-dependently suppressed B16-BL6 cell growth. In the cells cultured with SDF-1, a more potent suppression was observed. 4F-Benzoyl-TE14011 was rapidly released from 4F-benzoyl-TE14011-PLA for an initial period, both in vitro and in vivo. A steady release was thereafter observed. Therefore, this drug release profile might contribute to prevention of melanoma metastasis at the steps involving the migration and cell growth. These results also show that a sustained drug release formulation could be a useful drug delivery system for CXCR4 antagonists. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:226 / 232
页数:7
相关论文
共 37 条
[21]   Lecithinized superoxide dismutase: An inhibitor of human immunodeficiency virus replication [J].
Premanathan, M ;
Nakashima, H ;
Igarashi, R ;
Mizushima, Y ;
Yamada, K .
AIDS RESEARCH AND HUMAN RETROVIRUSES, 1997, 13 (04) :283-290
[22]   Expression of functional chemokine receptors CXCR3 and CXCR4 on human melanoma cells [J].
Robledo, MM ;
Bartolomé, RA ;
Longo, N ;
Rodríguez-Frade, JM ;
Mellado, M ;
Longo, I ;
van Muijen, GNP ;
Sánchez-Mateos, P ;
Teixidó, J .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (48) :45098-45105
[23]  
Taichman RS, 2002, CANCER RES, V62, P1832
[24]   A novel sustained-release formulation of insulin with dramatic reduction in initial rapid release [J].
Takenaga, M ;
Yamaguchi, Y ;
Kitagawa, A ;
Ogawa, Y ;
Mizushima, Y ;
Igarashi, R .
JOURNAL OF CONTROLLED RELEASE, 2002, 79 (1-3) :81-91
[25]   A novel insulin formulation can keep providing steady levels of insulin for much longer periods in-vivo [J].
Takenaga, M ;
Yamaguchi, Y ;
Kitagawa, A ;
Ogawa, Y ;
Mizushima, Y ;
Igarashi, R .
JOURNAL OF PHARMACY AND PHARMACOLOGY, 2002, 54 (09) :1189-1194
[26]   Enhancement of the T140-based pharmacophores leads to the development of more potent and bio-stable CXCR4 antagonists [J].
Tamamura, H ;
Hiramatsu, K ;
Mizumoto, M ;
Ueda, S ;
Kusano, S ;
Terakubo, S ;
Akamatsu, M ;
Yamamoto, N ;
Trent, JO ;
Wang, ZX ;
Peiper, SC ;
Nakashima, H ;
Otaka, A ;
Fujii, N .
ORGANIC & BIOMOLECULAR CHEMISTRY, 2003, 1 (21) :3663-3669
[27]   Development of specific CXCR4 inhibitors possessing high selectivity indexes as well as complete stability in serum based on an anti-HIV peptide T140 [J].
Tamamura, H ;
Omagari, A ;
Hiramatsu, K ;
Gotoh, K ;
Kanamoto, T ;
Xu, YN ;
Kodama, E ;
Matsuoka, M ;
Hattori, T ;
Yamamoto, N ;
Nakashima, H ;
Otaka, A ;
Fujii, N .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2001, 11 (14) :1897-1902
[28]   Synthesis of potent CXCR4 inhibitors possessing low cytotoxicity and improved biostability based on T140 derivatives [J].
Tamamura, H ;
Hiramatsu, K ;
Kusano, S ;
Terakubo, S ;
Yamamoto, N ;
Trent, JO ;
Wang, ZX ;
Peiper, SC ;
Nakashima, H .
ORGANIC & BIOMOLECULAR CHEMISTRY, 2003, 1 (21) :3656-3662
[29]   Synthesis and evaluation of pseudopeptide analogues of a specific CXCR4 inhibitor, T140:: The insertion of an (E)-alkene dipeptide isostere into the βII′-turn moiety [J].
Tamamura, H ;
Hiramatsu, K ;
Miyamoto, K ;
Omagari, A ;
Oishi, S ;
Nakashima, H ;
Yamamoto, N ;
Kuroda, Y ;
Nakagawa, T ;
Otaka, A ;
Fujii, N .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2002, 12 (06) :923-928
[30]   T140 analogs as CXCR4 antagonists identified as anti-metastatic agents in the treatment of breast cancer [J].
Tamamura, H ;
Hori, A ;
Kanzaki, N ;
Hiramatsu, K ;
Mizumoto, M ;
Nakashima, H ;
Yamamoto, N ;
Otaka, A ;
Fujii, N .
FEBS LETTERS, 2003, 550 (1-3) :79-83