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 downregulated N-cadherin and Vimentin. Oridonin inhibited the protein and mRNA levels of Snail and Slug. Furthermore, oridonin inhibited TGF-β-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-β1-induced EMT by inhibiting TGF-β1/Smad2/3 signaling pathway in osteosarcoma.

骨肉瘤是最常见的原发性骨肿瘤，具有高度浸润性和低长期生存率。最近，上皮-间质转化（EMT）被报道为癌症侵袭和转移的关键事件。Oridonin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EMT和骨肉瘤转移的作用尚不清楚。在这项研究中，我们调查了冬凌草甲素对EMT和骨肉瘤转移的潜在机制。我们发现冬凌草甲素抑制了MG-63和143B细胞的迁移和侵袭。此外，冬凌草甲素增加了E-钙黏着蛋白的蛋白质表达，而降低了N-钙黏着蛋白和波形蛋白的蛋白质表达。冬凌草甲素上调E-钙粘蛋白的转录，下调N-钙粘蛋白和波形蛋白。冬凌草甲素抑制蜗牛和Sl的蛋白质和mRNA水平。此外，冬凌草甲素抑制了TGF-β诱导的Smad 2/3的磷酸化，阻止了Smad二聚体易位到细胞核中。最后，我们建立了骨肉瘤143B细胞转移模型，并发现冬凌草甲素抑制了肺转移体内。冬凌草甲素增加了E-钙粘蛋白的蛋白质表达，并减少了N-钙粘蛋白和波形蛋白的表达。冬凌草甲素抑制Snail和Slug的蛋白质表达以及Smad 2/3活化。总之，我们的研究表明，冬凌草甲素通过抑制骨肉瘤中的TGF-β1/ Smad2 / 3信号通路来抑制EMT和TGF-β1诱导的EMT。