Hsin Chung-Han, Huang Cheng-Chen, Chen Pei-Ni, Hsieh Yih-Shou, Yang Shun-Fa, Ho Yu-Ting, Lin Chiao-Wen
* Department of Otolaryngology, Chung Shan Medical University Hospital, Taichung, Taiwan.
§ School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Am J Chin Med. 2017;45(7):1557-1572. doi: 10.1142/S0192415X17500847. Epub 2017 Sep 25.
Nasopharyngeal carcinoma (NPC) is characterized by a high incidence of metastasis in the neck lymph nodes, resulting in a poor prognosis and posing challenges for treatment. In this study, we investigated the in vitro antimetastatic properties of Rubus idaeus extract (RIE) on human nasopharyngeal carcinoma cells. HONE-1, NPC-39 and NPC-BM cells were subjected to RIE treatment, and effects on the migration and invasion of tumor cells were analyzed. The results showed that RIE suppressed the migration and invasion of NPC cells. Gelatin zymography assay, Western blotting and real-time PCR showed that matrix metalloproteinases-2 (MMP-2) enzyme activity, protein expression and mRNA levels were down-regulated by RIE treatment. To identify the signaling pathway, mitogen-activated protein kinase proteins were examined, which showed that phosphorylation of ERK1/2 was inhibited after the treatment of RIE. In summary, our data showed that RIE inhibited the migration and invasion of NPC cells by suppressing the expression of MMP-2 by down-regulating the ERK1/2 signaling pathway, suggesting that Rubus idaeus may serve as chemotherapeutic and chemopreventive agent for NPC.
鼻咽癌（NPC）的特点是颈部淋巴结转移发生率高，导致预后不良并给治疗带来挑战。在本研究中，我们研究了悬钩子提取物（RIE）对人鼻咽癌细胞的体外抗转移特性。对HONE-1、NPC-39和NPC-BM细胞进行RIE处理，并分析其对肿瘤细胞迁移和侵袭的影响。结果表明，RIE抑制了NPC细胞的迁移和侵袭。明胶酶谱分析、蛋白质印迹法和实时PCR表明，RIE处理下调了基质金属蛋白酶-2（MMP-2）的酶活性、蛋白质表达和mRNA水平。为了确定信号通路，检测了丝裂原活化蛋白激酶蛋白，结果表明，RIE处理后ERK1/2的磷酸化受到抑制。总之，我们的数据表明，RIE通过下调ERK1/2信号通路抑制MMP-2的表达，从而抑制NPC细胞的迁移和侵袭，这表明悬钩子可能作为鼻咽癌的化疗和化学预防剂。
