Shih Yung-Luen, Au Man-Kuan, Liu Ko-Lin, Yeh Ming-Yang, Lee Ching-Hsiao, Lee Mei-Hui, Lu Hsu-Feng, Yang Jiun-Long, Wu Rick Sai-Chuen, Chung Jing-Gung
Department of Pathology and Laboratory Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
School of Medical Laboratory Science and Biotechnology, Taipei Medical University, Taipei, Taiwan.
Environ Toxicol. 2017 Nov;32(11):2400-2413. doi: 10.1002/tox.22453. Epub 2017 Aug 10.
Ouabain, the specific Na /K -ATPase blocker, has biological activity including anti-proliferative and anti-metastasis effects in cancer cell. There is no study to show ouabain inhibiting cell migration and invasion in human osteosarcoma U-2 OS cells. Thus, we investigated the effect of ouabain on the cell migration and invasion of human osteosarcoma U-2 OS cells. Results indicated that ouabain significantly decreased the percentage of viable cells at 2.5-5.0 μM, thus, we selected 0.25-1.0 μM for inhibiting studies. Ouabain inhibited cell migration, invasion and the enzymatic activities of MMP-2, and also affected the expression of metastasis-associated protein in U-2 OS cells. The cDNA microarray assay indicated that CDH1, TGFBR3, SHC3 and MAP2K6 metastasis-related genes were increased, but CCND1, JUN, CDKN1A, TGFB1, 2 and 3, SMAD4, MMP13, MMP2 and FN1 genes were decreased. These findings provide more information regarding ouabain inhibited cell migration and invasion and associated gene expressions in U-2 OS cells after exposed to ouabain.
哇巴因,一种特异性的钠钾ATP酶阻滞剂,具有包括在癌细胞中的抗增殖和抗转移作用在内的生物学活性。尚无研究表明哇巴因能抑制人骨肉瘤U-2 OS细胞的迁移和侵袭。因此,我们研究了哇巴因对人骨肉瘤U-2 OS细胞迁移和侵袭的影响。结果表明,2.5 - 5.0 μM的哇巴因显著降低了活细胞百分比,因此,我们选择0.25 - 1.0 μM进行抑制研究。哇巴因抑制细胞迁移、侵袭以及MMP-2的酶活性,还影响U-2 OS细胞中转移相关蛋白的表达。cDNA微阵列分析表明,CDH1、TGFBR3、SHC3和MAP2K6等转移相关基因表达上调,但CCND1、JUN、CDKN1A、TGFB1、2和3、SMAD4、MMP13、MMP2和FN1基因表达下调。这些发现为哇巴因暴露后抑制U-2 OS细胞迁移和侵袭及相关基因表达提供了更多信息。