LJNK, an indoline-2,3-dione-based aminopeptidase N inhibitor with promising antitumor potency
LJNK, an indoline-2,3-dione-based aminopeptidase N inhibitor with promising antitumor potency
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LJNK，一种基于二氢吲哚-2,3-二酮的氨肽酶 N 抑制剂，具有良好的抗肿瘤功效
DOI：
10.1097/cad.0000000000000351
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发表时间：
2016-07-01
影响因子：
2.3
通讯作者：
Xu, Wenfang
中科院分区：
文献类型：
--
作者：
Hou, Jinning;Jin, Kang;Xu, Wenfang
在我们以前的研究中，我们发现LJNK具有很强的氨肽酶N（APN）抑制活性。在本研究中，我们进一步评估了LJNK在体外和体内的抗肿瘤作用。酶促实验表明，LJNK对人癌细胞表面APN和猪肾微粒体APN的抑制活性均优于bestatin。此外，LJNK还能抑制大鼠主动脉环微血管的生长和HUVEC管状结构的形成，其抗血管生成作用强于bestatin。[（3-[4，5-二甲基-2-噻唑基]-2，5-二苯基-2H-溴化四氮唑）]实验和克隆形成实验表明，LJNK在短期和长期均能抑制癌细胞的生长。在荷H22移植瘤小鼠体内证实了其抗肿瘤作用。Annexin V-异硫氰酸荧光素/碘化丙啶法显示LJNK可诱导28.1%的PLC/PRF/5细胞凋亡，western blot法证实了LJNK诱导PLC/PRF/5细胞凋亡的可能途径。上述结果表明，LJNK抑制细胞增殖和血管生成，并通过降低APN活性诱导细胞凋亡。
In our previous study, we found that LJNK showed potent aminopeptidase N (APN)-inhibitory activity. In the current study, we further evaluated the antitumor effects of LJNK both in vitro and in vivo. Enzyme experiments showed that LJNK showed better inhibitory activity than bestatin against APN both from human carcinoma cells’ surface and from porcine kidney microsomes. In addition, LJNK could suppress rat aortic ring microvessel growth and HUVEC tubular structure formation, which showed its stronger antiangiogenesis effects than bestatin. [(3-[4,5-Dimethyl-2-thiazolyl]-2,5-diphenyl-2H-tetrazolium bromide)] assay and clonogenic assay showed that LJNK suppressed cancer cell growth both in the short and the long term. Mice bearing H22 transplantation tumor proved its antitumor effects in vivo. Annexin V-fluorescein isothiocyanate/propidium iodide assay showed that LJNK could induce 28.1% PLC/PRF/5 cell apoptosis and the apoptotic pathway was probably identified by western blot. The above-mentioned results suggested that LJNK inhibited cell proliferation and angiogenesis, and induced apoptosis by decreasing APN activity.