Development of novel molecular-targeted medicine against aminopeptidase

本研究的目的是开发新型的癌细胞膜上过表达的氨肽酶N（APN）抑制剂，并评估其对癌细胞生长和血管生成的抑制作用。新合成的异羟肟酸衍生物24 F对HL 60细胞膜上表达的氨基肽酶活性有抑制作用。该化合物可抑制肝癌细胞株的生长和侵袭。此外，发现血管内皮细胞与24F的孵育对于抑制血管生成现象如迁移和管形成是有效的。此外，新合成的bestatin衍生物LYP也具有抑制癌细胞生长以及血管内皮细胞迁移和管形成的能力。这些结果表明，新合成的氨肽酶抑制剂通过抑制癌细胞侵袭和癌组织周围的血管生成而作为肝癌的抗癌剂是有效的。

This study was aimed to develop novel inhibitors of aminopeptidase N(APN) overexpressed on cancer cell membrane and to evaluate the suppressive effect on cancer cell growth and angiogenesis. A newly-synthesized compound 24F, one of hydroxamic acid derivatives, inhibited the activity of aminopeptidases expressed on HL60 cell membrane. This compound inhibited the growth and invasion of hepatoma cell lines. In addition, incubation of vascular endothelial cells with 24F was found to be effective for the suppression of the angiogenic phenomena such as migration and tube formation. Furthermore, a newly-synthesized bestatin derivative LYP also had the ability to inhibit cancer cell growth as well as migration and tube formation of vascular endothelial cells. These results suggest that newly-synthesized aminopeptidase inhibitors are effective as an anti-cancer agent for hepatoma via inhibition of cancer cell invasion and angiogenesis surrounding cancer tissue.