Oridonin prevents epithelial-mesenchymal transition and TGF-β1-induced epithelial-mesenchymal transition by inhibiting TGF-β1/Smad2/3 in osteosarcoma
Oridonin prevents epithelial-mesenchymal transition and TGF-β1-induced epithelial-mesenchymal transition by inhibiting TGF-β1/Smad2/3 in osteosarcoma
复制标题
DOI：
10.1016/j.cbi.2018.09.013
复制
发表时间：
2018-12-25
影响因子：
5.1
通讯作者：
Zhang, Qi
中科院分区：
文献类型：
--
作者：
Sun, Yang;Jiang, Xiubo;Zhang, Qi
骨肉瘤是最常见的原发骨肿瘤，具有侵袭性强、长期存活率低的特点。近年来，上皮-间充质转化(EMT)被认为是肿瘤侵袭和转移的关键事件。冬凌草甲素是一种具有生物活性的二萜类化合物，已被证明具有抗癌作用。然而，冬凌草甲素对骨肉瘤EMT和转移的影响尚不清楚。本研究旨在探讨冬凌草甲素对骨肉瘤内皮细胞转化和转移的作用机制。我们发现冬凌草甲素抑制MG-63和143B细胞的迁移和侵袭。冬凌草甲素增加E-钙粘蛋白的蛋白表达，降低N-钙粘蛋白和Vimentin的蛋白表达。冬凌草甲素上调E-钙粘蛋白的转录，下调N-钙粘蛋白和Vimentin的表达。冬凌草甲素能抑制蜗牛和鼻涕的蛋白质和mRNA水平。冬凌草甲素还可抑制转化生长因子-β诱导的Smad2/3的磷酸化，阻止Smad二聚体移位到细胞核内。最后，我们建立了骨肉瘤143B细胞的转移模型，发现冬凌草甲素对体内肺转移有抑制作用。冬凌草甲素可增加E-钙粘蛋白的蛋白表达，降低N-钙粘蛋白和波形蛋白的表达。冬凌草甲素抑制Snail和Slug蛋白的表达，并抑制Smad2/3的激活。综上所述，我们的研究表明冬凌草甲素通过抑制转化生长因子-β1/Smad2/3信号通路抑制骨肉瘤内膜转化和转化生长因子-β1诱导的转化。
Osteosarcoma is the most common primary bone tumor with highly invasive characteristic and low long-term survival. Recently, epithelial-mesenchymal transition (EMT) is reported as a key event in cancer invasion and metastasis. Oridonin, a bioactive diterpenoid, has been proved to possess anti-cancer effects. However, the effect of oridonin on EMT and metastasis of osteosarcoma is unclear. In this study, we investigated the underlying mechanism of oridonin on EMT and metastasis of osteosarcoma. We found that oridonin inhibited migration and invasion of MG-63 and 143B cells. Moreover, oridonin increased the protein expression of E-cadherin and decreased that of N-cadherin and Vimentin. Oridonin upregulated the transcription of E-cadherin and down-regulated N-cadherin and Vimentin. Oridonin inhibited the protein and mRNA levels of Snail and Slug. Furthermore, oridonin inhibited TGF-beta-induced phosphorylation of Smad 2/3, prevented Smad dimer translocation into the nucleus. Finally, we established metastatic models of osteosarcoma 143B cells, and found that oridonin inhibited lung metastasis in vivo. Oridonin increased the protein expression of E-cadherin and reduced N-cadherin and Vimentin. Oridonin inhibited the protein expression of Snail and Slug as well as Smad 2/3 activation. In conclusion, our study demonstrated that oridonin inhibited EMT and TGF-beta 1-induced EMT by inhibiting TGF-beta 1/Smad2/3 signaling pathway in osteosarcoma.