Park Jun Yeon, Park Do Hwi, Jeon Youngsic, Kim Young-Joo, Lee Jaemin, Shin Myoung-Sook, Kang Ki Sung, Hwang Gwi Seo, Kim Hyun Young, Yamabe Noriko
Department of Food Science and Biotechnology, Kyonggi University, Suwon 16227, Republic of Korea.
College of Korean Medicine, Gachon University, Seongnam 13120, Republic of Korea.
Bioorg Med Chem Lett. 2018 Oct 15;28(19):3150-3154. doi: 10.1016/j.bmcl.2018.08.034. Epub 2018 Aug 28.
Metastasis is responsible for the great majority of deaths in cancer patients. Matrix metalloproteinases (MMPs) have critical functions in cancer metastasis. Especially, MMP-2 and MMP-9 play a major role in tumor-cell migration and invasion. Therefore, to first find out the inhibitory effect of eupatilin on expression of MMPs in SNU182 cells, we used quantitative real-rime PCR to measure MMP-2 and MMP-9 mRNA levels. Eupatilin suppressed transcription of MMP-2 in SNU182 cells more than did the corresponding controls. Also, eupatilin significantly blocked tube formation when treated with a concentration of 3.125 or 6.25 μg/mL on human umbilical vein vascular endothelial cells (HUVECs). Eupatilin induced significant anti-angiogenic potential associated with down-regulation of hypoxia-inducible factor 1-alpha (HIF-1α), vascular endothelial growth factor (VEGF), and phosphorylated Akt expression. Thus, tube-formation inhibition and MMP-2-mediated migration are likely to be important therapeutic targets of eupatilin in hepatocellular carcinoma metastasis.
转移是导致癌症患者死亡的主要原因。基质金属蛋白酶（MMPs）在癌症转移中发挥着关键作用。特别是，MMP-2和MMP-9在肿瘤细胞迁移和侵袭中起主要作用。因此，为了首先了解泽兰素对SNU182细胞中MMPs表达的抑制作用，我们使用定量实时PCR来测量MMP-2和MMP-9的mRNA水平。泽兰素比相应的对照更能抑制SNU182细胞中MMP-2的转录。此外，当用3.125或6.25μg/mL的浓度处理人脐静脉血管内皮细胞（HUVECs）时，泽兰素显著阻断了管腔形成。泽兰素诱导了与缺氧诱导因子1-α（HIF-1α）、血管内皮生长因子（VEGF）和磷酸化Akt表达下调相关的显著抗血管生成潜力。因此，管腔形成抑制和MMP-2介导的迁移可能是泽兰素在肝细胞癌转移中的重要治疗靶点。
