Ursolic acid inhibits epithelial-mesenchymal transition by suppressing the expression of astrocyte-elevated gene-1 in human nonsmall cell lung cancer A549 cells
Ursolic acid inhibits epithelial-mesenchymal transition by suppressing the expression of astrocyte-elevated gene-1 in human nonsmall cell lung cancer A549 cells
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DOI：
10.1097/cad.0b013e328360093b
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发表时间：
2013-06-01
影响因子：
2.3
通讯作者：
Zhao, Wei
中科院分区：
文献类型：
--
作者：
Liu, Kunmei;Guo, Le;Zhao, Wei
肺癌是世界上与死亡相关程度最高的癌症之一。熊果酸（UA）是一种五环三萜酸，具有促进细胞凋亡、抗血管生成、抗肿瘤转移等多种抗癌作用。本研究旨在探讨UA对肺癌A549细胞转移的抑制机制。首先，通过黏附实验、细胞伤口愈合实验和体外跨井迁移实验，我们发现UA以浓度依赖的方式抑制肺癌细胞的转移。此外，UA处理A549细胞后，星形细胞升高基因-1 （AEG-1）表达降低，E-cadherin上调，N-cadherin和vimentin下调，这是上皮-间质转化（EMT）的特征。进一步的结果也证实，通过siRNA技术直接敲低AEG-1的表达，可以降低vimentin的表达，表明AEG-1参与了ua介导的EMT抑制。此外，我们的研究结果表明，UA通过抑制核因子- jb信号传导来抑制AEG-1的表达水平。总之，UA通过抑制A549细胞中AEG-1的表达来抑制EMT，这与抑制核因子- jb有关。这些发现提示UA是一种有效的抗肺癌药物，可能具有阻止肺癌细胞侵袭和转移的作用。抗癌药物24:494-503 (C) 2013 Wolters Kluwer Health垂直bar Lippincott Williams & Wilkins。抗癌药物，2013,24 (4):494-503
Lung cancer is one of the most death-related cancers worldwide. Ursolic acid (UA), a pentacyclic triterpene acid, has a wide range of anticancer functions such as proapoptosis, antiangiogenesis, and antimetastasis. This study was carried out to explore the inhibition mechanism of UA on metastasis of lung cancer A549 cells. First, we found that UA inhibited the metastasis of lung cancer cells in a concentration-dependent manner through an adhesion assay, a cell wound healing assay, and a transwell migration assay in vitro. In addition, after treatment with UA, the A549 cells showed decreased expression of astrocyteelevated gene-1 (AEG-1) accompanied by upregulation of E-cadherin and downregulation of N-cadherin and vimentin, which have been reported to characterize the epithelial-mesenchymal transition (EMT). Further results also confirmed that the expression of vimentin was decreased by the siRNA technique to directly knock down AEG-1 expression, indicating that AEG-1 was involved in UA-mediated EMT inhibition. Furthermore, our results showed that UA suppressed the expression level of AEG-1 by repressing nuclear factor-jB signaling. Altogether, UA inhibited the EMT by suppressing the expression of AEG-1, correlating with inhibition of nuclear factor-jB in A549 cells. These findings suggested that UA was a potent anti-lung cancer agent, and it may be able to prevent invasion and metastasis of lung cancer cells. Anti-Cancer Drugs 24:494-503 (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. Anti-Cancer Drugs 2013, 24:494-503