Chen Yang-Yu, Hsieh Ming-Ju, Hsieh Yih-Shou, Chang Yu-Chao, Chen Pei-Ni, Yang Shun-Fa, Ho Hsin-Yu, Chou Ying-Erh, Lin Chiao-Wen
Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan.
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Environ Toxicol. 2017 Oct;32(10):2287-2294. doi: 10.1002/tox.22444. Epub 2017 Jul 5.
Rheum palmatum L., a traditional Chinese medication, has been used for the treatment of various disorders. However, the detailed impacts and underlying mechanisms of R. palmatum L. extracts (RLEs) on human oral cancer cell metastasis are still unclear. Here, we tested the hypothesis that an RLE has antimetastatic effects on SCC-9 and SAS human oral cancer cells. Gelatin zymography, Western blot, real-time polymerase chain reaction, and luciferase assay were used to explore the underlying mechanisms involved in the antimetastatic effects on oral cancer cells. Our results revealed that the RLE (up to 20 μg/mL, without cytotoxicity) attenuated SCC-9 and SAS cell motility, invasiveness, and migration by reducing matrix metalloproteinase (MMP)-2 enzyme activities. Western blot analysis of the MAPK signaling pathway indicated that the RLE significantly decreased phosphorylated ERK1/2 levels but not p38 and JNK levels. In conclusion, RLEs exhibit antimetastatic activity against oral cancer cells through the transcriptional repression of MMP-2 via the Erk1/2 signaling pathways. Thus, RLEs may be potentially useful as antimetastatic agents for oral cancer chemotherapy.
大黄是一种传统中药,已被用于治疗各种疾病。然而,大黄提取物(RLEs)对人口腔癌细胞转移的具体影响和潜在机制仍不清楚。在此,我们检验了RLE对SCC-9和SAS人口腔癌细胞具有抗转移作用这一假设。采用明胶酶谱法、蛋白质免疫印迹法、实时聚合酶链反应和荧光素酶测定法来探究RLE对口腔癌细胞抗转移作用的潜在机制。我们的结果显示,RLE(浓度高达20μg/mL,无细胞毒性)通过降低基质金属蛋白酶(MMP)-2酶活性减弱了SCC-9和SAS细胞的运动性、侵袭性和迁移能力。对MAPK信号通路的蛋白质免疫印迹分析表明,RLE显著降低了磷酸化ERK1/2的水平,但未降低p38和JNK的水平。总之,RLEs通过Erk1/2信号通路对MMP-2进行转录抑制,从而表现出对口腔癌细胞的抗转移活性。因此,RLEs可能作为口腔癌化疗的抗转移药物具有潜在用途。