Yu Chao, Chen Lili, Yie Lin, Wei Lei, Wen Taoyu, Liu Yanan, Chen Hongyan
Department of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, P.R. China.
Oncol Rep. 2015 May;33(5):2402-10. doi: 10.3892/or.2015.3834. Epub 2015 Mar 4.
High expression levels of the forkhead box M1 (FoxM1) transcription factor are associated with metastasis and poor prognosis of malignancies. However, little is known concerning its function in nasopharyngeal carcinoma (NPC). The present study aimed to investigate the impact of FoxM1 inhibition on the migration and invasion of NPC cells and the potential mechanisms. The effects of FoxM1 inhibitor treatment and FoxM1 silencing on the proliferation, migration and invasion of NPC CNE-1 and CNE-2 cells were examined by CCK-8, Transwell migration/invasion and colony formation assays. The effects of stable FoxM1 silencing on the growth and lung metastasis of implanted NPC were evaluated. The relative levels of FoxM1, zinc finger E-box binding homeobox 2 (ZEB2), Snail2 and E-cadherin in the different groups of NPC cells and tumors were determined by quantitative real-time PCR, western blotting and immunohistochemical assays. Treatment with thiostrepton, FoxM1 inhibitor, significantly reduced the survival of NPC cells. Treatment with thiostrepton and/or knockdown of FoxM1 inhibited the anchorage-independent proliferation, migration and invasion of NPC cells. Inhibition of FoxM1 also increased the relative levels of E-cadherin, but reduced ZEB2 and Snail2 expression in NPC cells. Stable FoxM1 silencing inhibited the growth and lung metastasis of implanted NPC in vivo, which was associated with increased levels of E-cadherin, but decreased ZEB2 and Snail2 expression in the NPC tumors. In conclusion, our data clearly indicate that knockdown of FoxM1 inhibited the growth and metastasis of human NPC by modulating epithelial-to-mesenchymal transition (EMT), and FoxM1 may be a potential target for the intervention of NPC.
叉头框M1（FoxM1）转录因子的高表达水平与恶性肿瘤的转移和不良预后相关。然而，关于其在鼻咽癌（NPC）中的功能知之甚少。本研究旨在探讨抑制FoxM1对NPC细胞迁移和侵袭的影响及其潜在机制。通过CCK-8、Transwell迁移/侵袭和集落形成实验检测FoxM1抑制剂处理和FoxM1沉默对NPC CNE-1和CNE-2细胞增殖、迁移和侵袭的影响。评估稳定沉默FoxM1对植入性NPC生长和肺转移的影响。通过定量实时PCR、蛋白质免疫印迹和免疫组织化学实验测定不同组NPC细胞和肿瘤中FoxM1、锌指E盒结合同源框2（ZEB2）、Snail2和E-钙黏蛋白的相对水平。硫链丝菌素（一种FoxM1抑制剂）处理显著降低了NPC细胞的存活率。硫链丝菌素处理和/或敲低FoxM1抑制了NPC细胞的非锚定依赖性增殖、迁移和侵袭。抑制FoxM1还增加了NPC细胞中E-钙黏蛋白的相对水平，但降低了ZEB2和Snail2的表达。稳定沉默FoxM1在体内抑制了植入性NPC的生长和肺转移，这与NPC肿瘤中E-钙黏蛋白水平升高、ZEB2和Snail2表达降低有关。总之，我们的数据清楚地表明，敲低FoxM1通过调节上皮-间质转化（EMT）抑制了人NPC的生长和转移，并且FoxM1可能是NPC干预的潜在靶点。
