Yeh Chao-Bin, Yu Yung-Luen, Lin Chiao-Wen, Chiou Hui-Ling, Hsieh Ming-Ju, Yang Shun-Fa
Cancer Research Center, Changhua Christian Hospital, Changhua, Taiwan.
BMC Complement Altern Med. 2014 Apr 30;14:141. doi: 10.1186/1472-6882-14-141.
The survival rate of malignant tumors, and especially hepatocellular carcinoma (HCC), has not improved primarily because of uncontrolled metastasis. In our previous studies, we have reported that Terminalia catappa leaf extract (TCE) exerts antimetastasis effects on HCC cells. However, the molecular mechanisms of urokinase-type plasminogen activator (u-PA) in HCC metastasis have not been thoroughly investigated, and remain poorly understood.
The activities and protein levels of u-PA were determined by casein zymography and western blotting. Transcriptional levels of u-PA were detected by real-time PCR and promoter assays.
We found that treatment of Huh7 cells with TCE significantly reduced the activities, protein levels and mRNA levels of u-PA. A chromatin immunoprecipitation (ChIP) assay showed that TCE inhibited the transcription protein of nuclear factors SP-1 and NF-κB. TCE also did inhibit the effects of u-PA by reducing the phosphorylation of ERK1/2 pathway.
These results show that u-PA expression may be a potent therapeutic target in the TCE-mediated suppression of HCC metastasis.
恶性肿瘤，尤其是肝细胞癌（HCC）的生存率尚未得到改善，主要原因是转移无法得到控制。在我们之前的研究中，我们报道了榄仁树叶提取物（TCE）对肝癌细胞具有抗转移作用。然而，尿激酶型纤溶酶原激活剂（u-PA）在肝癌转移中的分子机制尚未得到充分研究，仍知之甚少。
通过酪蛋白酶谱法和蛋白质印迹法测定u-PA的活性和蛋白水平。通过实时PCR和启动子分析检测u-PA的转录水平。
我们发现用TCE处理Huh7细胞可显著降低u-PA的活性、蛋白水平和mRNA水平。染色质免疫沉淀（ChIP）分析表明，TCE抑制核因子SP-1和NF-κB的转录蛋白。TCE还通过降低ERK1/2途径的磷酸化来抑制u-PA的作用。
这些结果表明，u-PA表达可能是TCE介导的抑制肝癌转移的有效治疗靶点。
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