静脉注射杂交脂质体在体内异种移植结直肠癌小鼠模型中抑制肝转移。

Intravenous injection of hybrid liposomes suppresses the liver metastases in xenograft mouse models of colorectal cancer in vivo.

机构信息

Division of Applied Life Science, Graduate School of Engineering, Sojo University, 4-22-1 Ikeda, Nishi-ku, Kumamoto 860-0082 Japan.

出版信息

Eur J Med Chem. 2012 Nov;57:143-8. doi: 10.1016/j.ejmech.2012.08.040. Epub 2012 Sep 7.

DOI:10.1016/j.ejmech.2012.08.040

PMID:23059544

Abstract

Therapeutic effects of hybrid liposomes (HL) composed of l-α-dimyristoylphosphatidylcholine (DMPC) and polyoxyethylene(25) dodecyl ether (C(12)(EO)(25)) on the metastasis of human colon carcinoma (HCT116) cells were examined in vivo. Remarkably high therapeutic effects were obtained in the xenograft mouse models of colorectal cancer (CRC) liver metastases after treatment with HL-25 on the basis of relative liver weight and histological analysis of the liver tissue sections of mouse models with HE staining, and TUNEL staining for detection of apoptotic cells. The survival effects of HL-25 were obtained using xenograft mouse models of CRC liver metastases. Furthermore, with regard to pharmacokinetics, the accumulation of fluorescent labeled HL-25 was observed in the liver tissue of xenograft mouse models of CRC liver metastases for 24 h after the intravenous injection of fluorescent labeled HL-25. Therapeutic effects of HL without any drugs on the liver metastasis of human CRC were revealed for the first time in vivo.

摘要

研究了由 l-α-二肉豆蔻酰磷脂酰胆碱（DMPC）和聚氧乙烯（25）十二烷基醚（C（12）（EO）（25））组成的混合脂质体（HL）对人结肠癌细胞（HCT116）转移的治疗作用。在基于相对肝重和对用 HE 染色的小鼠模型的肝组织切片的组织学分析的结直肠癌（CRC）肝转移的异种移植小鼠模型中，在用 HL-25 处理后，观察到显著的高治疗效果，并且用 TUNEL 染色检测凋亡细胞。使用结直肠癌肝转移的异种移植小鼠模型获得了 HL-25 的生存效果。此外，关于药代动力学，在静脉注射荧光标记的 HL-25 后 24 h，在结直肠癌肝转移的异种移植小鼠模型的肝组织中观察到荧光标记的 HL-25 的积累。首次在体内揭示了 HL 对人 CRC 肝转移无任何药物治疗的治疗作用。