Epithelial-mesenchymal transition, a novel target of sulforaphane via COX-2/MMP2, 9/Snail, ZEB1 and miR-200c/ZEB1 pathways in human bladder cancer cells
Epithelial-mesenchymal transition, a novel target of sulforaphane via COX-2/MMP2, 9/Snail, ZEB1 and miR-200c/ZEB1 pathways in human bladder cancer cells
复制标题
上皮-间质转化，萝卜硫素通过 COX-2/MMP2、9/Snail、ZEB1 和 miR-200c/ZEB1 通路在人膀胱癌细胞中的新靶点
DOI：
10.1016/j.jnutbio.2012.08.004
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发表时间：
2013-06-01
影响因子：
5.6
通讯作者：
Wang, Shuran
中科院分区：
文献类型：
--
作者：
Shan, Yujuan;Zhang, Lanwei;Wang, Shuran
膀胱癌的转移和复发是其预后差、死亡率高的主要原因。萝卜硫素是一种仅存在于十字花科蔬菜中的植物化学物质，由于其生物活性和在尿液中的高代谢积累，具有预防膀胱癌的强大而特殊的潜力。在这篇论文中，萝卜硫素被证明可以显着抑制多种生化途径，包括恶性移行性膀胱癌T24细胞的附着、侵袭、迁移和趋化运动。用环氧合酶-2 (COX-2) 过表达质粒转染很大程度上消除了萝卜硫素对 MMP2/9 表达的抑制以及细胞侵袭能力。此外，萝卜硫素通过减少 ZEB1 和 Snail 等转录抑制因子，抑制上皮间质转化 (EMT) 过程，该过程是 E-钙粘蛋白诱导介导的肿瘤细胞侵袭和迁移的基础。在 COX-2 和/或 MMP2/9 过度表达的条件下，萝卜硫素仍然能够诱导 E-钙粘蛋白或减少 Snail/ZEB1 表达，表明可能涉及其他途径。进一步的研究表明，miR-200c 通过 ZEB1 阻遏物而不是 Snail 阻遏物在 E-钙粘蛋白的调节中发挥作用。总之，EMT 和两条公认的信号通路（COX-2/MMP2,9/ZEB1、Snail 和 miR-200c/ZEB1）都是萝卜硫素的靶点。这项研究表明萝卜硫素可能具有预防人类膀胱癌复发的治疗潜力。 (C) 2013 Elsevier Inc. 保留所有权利。
Metastasis and recurrence of bladder cancer are the main reasons for its poor prognosis and high mortality rates. Because of its biological activity and high metabolic accumulation in urine, sulforaphane, a phytochemical exclusively occurring in cruciferous vegetables, has a powerful and specific potential for preventing bladder cancer. In this paper, sulforaphane is shown to significantly suppress a variety of biochemical pathways including the attachment, invasion, migration and chemotaxis motion in malignant transitional bladder cancer T24 cells. Transfection with cyclooxygenase-2 (COX-2) overexpression plasmid largely abolished inhibition of MMP2/9 expression as well as cell invasive capability by sulforaphane. Moreover, sulforaphane inhibited the epithelial-to-mesenchymal transition (EMT) process which underlies tumor cell invasion and migration mediated by E-cadherin induction through reducing transcriptional repressors, such as ZEB1 and Snail. Under conditions of over-expression of COX-2 and/or MMP2/9, sulforaphane was still able to induce E-cadherin or reduce Snail/ZEB1 expression, suggesting that additional pathways might be involved. Further studies indicated that miR-200c played a role in the regulation of E-cadherin via the ZEB1 repressor but not by the Snail repressor. In conclusion, the EMT and two recognized signaling pathways (COX-2/MMP2,9/ ZEB1, Snail and miR-200c/ZEB1) are all targets for sulforaphane. This study indicated that sulforaphane may possess therapeutic potential in preventing recurrence of human bladder cancer. (C) 2013 Elsevier Inc. All rights reserved.