A single treatment with microcapsules containing a CXCR4 antagonist suppresses pulmonary metastasis of murine melanoma
A single treatment with microcapsules containing a CXCR4 antagonist suppresses pulmonary metastasis of murine melanoma
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DOI：
10.1016/j.bbrc.2004.05.155
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发表时间：
2004-07-16
影响因子：
3.1
通讯作者：
Igarashi, R
中科院分区：
文献类型：
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作者：
Takenaga, M;Tamamura, H;Igarashi, R
制备了含有CXCR4拮抗剂（4F-苯甲酰基-TE14011）的可生物降解的聚D,L-乳酸（PLA，分子量：约5000）微胶囊（4F-苯甲酰基-TE14011-PLA），并在小鼠中评估了其抗转移活性。单次皮下注射 4F-苯甲酰基-TE14011-PLA 可显着减少表达 CXCR4 的 B16-BL6 黑色素瘤细胞肺转移形成的集落数量。相同剂量的 4F-苯甲酰基-TE14011 在单次或一系列治疗中影响很小。 4F-苯甲酰基-TE14011 物质剂量依赖性地抑制 B16-BL6 细胞生长。在用 SDF-1 培养的细胞中，观察到更有效的抑制。在体外和体内，4F-苯甲酰-TE14011 在初始阶段均从 4F-苯甲酰-TE14011-PLA 中快速释放。此后观察到稳定释放。因此，这种药物释放曲线可能有助于在涉及迁移和细胞生长的步骤中预防黑色素瘤转移。这些结果还表明持续药物释放制剂可能是 CXCR4 拮抗剂的有用药物递送系统。 (C) 2004 Elsevier Inc. 保留所有权利。
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.