Negative regulation of transcription factor FoxM1 by p53 enhances oxaliplatin-induced senescence in hepatocellular carcinoma
Negative regulation of transcription factor FoxM1 by p53 enhances oxaliplatin-induced senescence in hepatocellular carcinoma
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p53对转录因子FoxM1的负调控增强奥沙利铂诱导的肝细胞癌衰老
DOI：
10.1016/j.canlet.2012.12.008
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发表时间：
2013-04-30
期刊：
影响因子：
9.7
通讯作者：
Liu, Peijun
中科院分区：
文献类型：
--
作者：
Qu, Kai;Xu, Xinsen;Liu, Peijun
以往的研究表明转录因子叉头盒M1（FoxM1）参与肝细胞癌（HCC）的细胞衰老。在本研究中，我们发现奥沙利铂可以诱导肝癌细胞衰老，因为FoxM1表达较低的晚期肝癌患者对奥沙利铂治疗更敏感。我们的数据表明，由于p53的抑制，FoxM1通过调节细胞周期相关蛋白p21，p27，细胞周期蛋白B1和D1在奥沙利铂诱导的衰老中发挥关键作用。此外，FoxM1的抑制，奥沙利铂处理，可以显着促进肝癌细胞的衰老。综上所述，我们的研究结果表明，FoxM1可能代表了一个有前途的治疗靶点，用于治疗HCC患者对奥沙利铂的化疗敏感性。(C)2012爱思唯尔爱尔兰有限公司保留所有权利。
Previous studies have demonstrated the involvement of transcriptional factor forkhead box M1 (FoxM1) in cellular senescence of hepatocellular carcinoma (HCC). In the present study, we revealed that oxaliplatin could induce senescence in HCC cells, since advanced HCC patients with lower expression of FoxM1 were more sensitive to oxaliplatin therapy. Our data indicated that due to the repression by p53, FoxM1 played a critical role in oxaliplatin-induced senescence via regulating cycle-related proteins p21, p27, cyclins B1 and D1. Furthermore, inhibition of FoxM1, combined with oxaliplatin treatment, could significantly promote the senescence of HCC cells. Taken together, our findings suggest that FoxM1 may represent a promising therapeutic target for the medication of the chemosensitivity to oxaliplatin in HCC patients. (C) 2012 Elsevier Ireland Ltd. All rights reserved.