FoxM1表达增加是二甲双胍抑制前列腺癌上皮-间质转化的作用靶点。
Increased FoxM1 expression is a target for metformin in the suppression of EMT in prostate cancer.
作者信息
Wang Yiru, Yao Binwei, Wang Yu, Zhang Mingbo, Fu Shuai, Gao Hanjing, Peng Ruiyun, Zhang Lingqiang, Tang Jie
机构信息
Department of Ultrasound, Chinese PLA General Hospital, Beijing 100853, P.R. China.
Department of Experimental Pathology, Beijing Institute of Radiation Medicine, Beijing 100850, P.R. China.
出版信息
Int J Mol Med. 2014 Jun;33(6):1514-22. doi: 10.3892/ijmm.2014.1707. Epub 2014 Mar 20.
Forkhead box M1 (FoxM1) transcription factor is related to the pathogenesis of various malignancies and recent evidence indicates that FoxM1 promotes epithelial-mesenchymal transition (EMT) in breast cancer. Metformin can inhibit the progression of cancer. However, whether FoxM1 plays a role in EMT in prostate cancer (PCa) and whether metformin can suppress EMT through FoxM1 in PCa remain unresolved issues. In this study, we investigated the expression levels of the FoxM1 protein in 62 PCa and 39 benign prostate hyperplasia (BPH) samples and found that the expression levels of FoxM1 were higher in the PCa tissues (66.1%) compared with the BPH tissues (28.2%) (p<0.05). We observed that FoxM1 was expressed in the PCa cell lines and that metformin suppressed cell proliferation and the expression of FoxM1. We induced EMT in the PCa cells by the addition of transforming growth factor (TGF)-β1 and verified the process by examining EMT-related gene (E-cadherin, vimentin and Slug) expression. In addition, the knockdown of FoxM1 by shRNA in the PCa cells reversed EMT and markedly reduced cell migration. These results indicate that metformin suppresses EMT by inhibiting FoxM1. We demonstrate that the suppression of FoxM1 may be an effective therapeutic strategy for PCa and provide further evidence of the anticancer effects of metformin.
叉头框M1(FoxM1)转录因子与多种恶性肿瘤的发病机制相关,最近的证据表明,FoxM1促进乳腺癌的上皮-间质转化(EMT)。二甲双胍可抑制癌症进展。然而,FoxM1在前列腺癌(PCa)的EMT中是否起作用以及二甲双胍是否能通过FoxM1抑制PCa的EMT仍是未解决的问题。在本研究中,我们检测了62例PCa样本和39例良性前列腺增生(BPH)样本中FoxM1蛋白的表达水平,发现与BPH组织(28.2%)相比,PCa组织中FoxM1的表达水平更高(66.1%)(p<0.05)。我们观察到FoxM1在PCa细胞系中表达,且二甲双胍可抑制细胞增殖和FoxM1的表达。我们通过添加转化生长因子(TGF)-β1诱导PCa细胞发生EMT,并通过检测EMT相关基因(E-钙黏蛋白、波形蛋白和Slug)的表达来验证该过程。此外,通过shRNA敲低PCa细胞中的FoxM1可逆转EMT并显著降低细胞迁移。这些结果表明,二甲双胍通过抑制FoxM1来抑制EMT。我们证明抑制FoxM1可能是PCa的一种有效治疗策略,并为二甲双胍的抗癌作用提供了进一步的证据。