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氯化两面针碱通过抑制 AKT 信号通路抑制肾癌细胞转移。

Nitidine chloride inhibits renal cancer cell metastasis via suppressing AKT signaling pathway.

机构信息

Department of Urology, Qilu Hospital of Shandong University, Ji'nan, Shandong, China; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University, Ji'nan, Shandong, China.

出版信息

Food Chem Toxicol. 2013 Oct;60:246-51. doi: 10.1016/j.fct.2013.07.062. Epub 2013 Jul 31.

DOI:10.1016/j.fct.2013.07.062
PMID:23911800
Abstract

Nitidine Chloride (NC) has been shown to have anti-cancer effects on various tumors. However, whether NC could exert anti-metastasis activity in renal cancer cells and the underlying mechanisms have not been elucidated. In this work, our data demonstrated the anti-metastasis effects of NC on renal cancer cells in vitro. With scratch assay and transwell assays, we found that NC potently suppressed the migration and invasion of 786-O and A498 cells. Mechanistically, we presented that NC significantly decreased phosphorylation of AKT, accompanied by down-regulation of MMP-2 and MMP-9. Furthermore, a specific AKT inhibitor, LY294002, could enhance the anti-metastasis effects of NC, which indicated that NC suppressed metastasis of renal cancer cells partly via inhibition of AKT activity. Taken together, our results imply that NC can be developed as a potential anti-metastasis agent to renal cancer.

摘要

氯化两面针碱(NC)已被证明对各种肿瘤具有抗癌作用。然而,NC 是否能在肾癌细胞中发挥抗转移活性及其潜在机制尚未阐明。在这项工作中,我们的数据表明 NC 在体外对肾癌细胞具有抗转移作用。通过划痕实验和 Transwell 实验,我们发现 NC 能强烈抑制 786-O 和 A498 细胞的迁移和侵袭。从机制上讲,我们发现 NC 显著降低了 AKT 的磷酸化水平,同时下调了 MMP-2 和 MMP-9。此外,一种特异性的 AKT 抑制剂 LY294002 可以增强 NC 的抗转移作用,这表明 NC 通过抑制 AKT 活性部分抑制了肾癌细胞的转移。综上所述,我们的研究结果表明 NC 可以作为一种潜在的抗肾癌细胞转移药物进行开发。

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