Evaluation of antitumor activities of hyaluronate binding antitumor drugs: Synthesis, characterization and antitumor activity
Evaluation of antitumor activities of hyaluronate binding antitumor drugs: Synthesis, characterization and antitumor activity
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DOI：
10.3109/10611869609046255
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发表时间：
1996-01-01
影响因子：
4.5
通讯作者：
Tatekawa, I
中科院分区：
文献类型：
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作者：
Akima, K;Ito, H;Tatekawa, I
为了增强抗肿瘤药物通过透明质酸（HA）受体（CD44）选择性递送到局部淋巴结和癌组织，我们合成了HA-丝裂霉素C复合物和HA-表柔比星复合物。为了研究HA在局部淋巴结的特异性分布，并评估HA受体在lewis肺癌细胞上的作用，我们还合成了c -14标记HA和荧光HA （FR-HA）。在大鼠体内进行了C-14-HA和ha -表柔比星复合物的代谢研究。sc治疗后观察两种化合物在淋巴结的特异性分布。采用体外荧光HA （FR-HA）技术研究了透明质酸（HA）经HA受体进入肺癌细胞的内化机制。观察到FR-HA与细胞表面结合后的内化。极低剂量（0.01 mg/kg） ha -丝裂霉素C （MMC）对移植小鼠lewis肺癌有明显的抗转移作用，而游离MMC则无明显的抗转移作用。
To enhance the selective delivery of antitumor drugs into regional lymph nodes and cancerous tissues via a hyaluronate (HA) receptor (CD44), we synthesized HA-mitomycin C complex and HA-epirubicin complex. To investigate the specific distribution of HA into regional lymph nodes and to evaluate the HA receptor on lewis lung carcinoma cells, we also synthesized C-14-labelled HA and fluorescent HA (FR-HA). The metabolic studies of C-14-HA and HA-epirubicin complex were performed in rats. The specific distribution of both compounds to the lymph nodes were observed after sc treatment. Internalization mechanism of HA into carcinoma cells (lewis lung carcinoma) via HA receptor was investigated using fluorescent HA (FR-HA) in vitro. Internalization of FR-HA following binding to the cell surfaces was observed. HA-Mitomycin C (MMC) exhibited potent anti-metastatic effects against lewis lung carcinoma implanted in mice at an extremely low dose (0.01 mg/kg) whereas free MMC had no effects.