1. Glaucocalyxin A reverses EMT and TGF-β1-induced EMT by inhibiting TGF-β1/Smad2/3 signaling pathway in osteosarcoma.
- Author
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Jiang X, Zhang Z, Song C, Deng H, Yang R, Zhou L, Sun Y, and Zhang Q
- Subjects
- Animals, Bone Neoplasms metabolism, Bone Neoplasms pathology, Cadherins metabolism, Cell Line, Tumor, Cell Movement drug effects, Diterpenes, Kaurane chemistry, Diterpenes, Kaurane therapeutic use, Humans, Lung Neoplasms drug therapy, Lung Neoplasms secondary, Mice, Mice, Nude, Osteosarcoma metabolism, Osteosarcoma pathology, Phosphorylation drug effects, Smad2 Protein metabolism, Smad3 Protein metabolism, Vimentin metabolism, Diterpenes, Kaurane pharmacology, Epithelial-Mesenchymal Transition drug effects, Signal Transduction drug effects, Transforming Growth Factor beta1 pharmacology
- Abstract
Metastatic osteosarcoma usually has an unsatisfactory response to the current standard chemotherapy and causes poor prognosis. Currently, epithelial-mesenchymal transition (EMT) is reported as a critical event in osteosarcoma metastasis. Glaucocalyxin A, a bioactive ent-kauranoid diterpenoid, exerts anti-cancer effect on osteosarcoma by inducing apoptosis in previous study. However, the effect of Glaucocalyxin A on EMT and metastasis of osteosarcoma is unclear. In this study, we investigated the potential mechanisms of Glaucocalyxin A on EMT and metastasis of osteosarcoma. We found that Glaucocalyxin A inhibited migration and invasion of MG-63 and 143B cells. Moreover, Glaucocalyxin A increased the protein and mRNA levels of E-cadherin and decreased the protein and transcription expression of N-cadherin, Vimentin. Glaucocalyxin A also inhibited the protein and mRNA levels of EMT-associated transcription factor including Snail and Slug. Furthermore, Glaucocalyxin A inhibited transforming growth factor-β1 (TGF-β1)-induced migration, invasion and EMT of low-metastatic osteosarcoma U2OS cells. Glaucocalyxin A inhibited TGF-β-induced phosphorylation of Smad 2/3 in osteosarcoma U2OS cells. Finally, we established transplanted metastatic models of highly metastatic osteosarcoma 143B cells. Glaucocalyxin A inhibited lung metastasis in vivo. Interestingly, Glaucocalyxin A increased the protein expression of E-cadherin and reduced the protein expression of N-cadherin and Vimentin. Glaucocalyxin A inhibited the protein expression of Snail and Slug in vivo. In summary, this study demonstrated that Glaucocalyxin A inhibited EMT and TGF-β1-induced EMT by inhibiting TGF-β1/Smad2/3 signaling pathway in osteosarcoma. Therefore, Glaucocalyxin A might be a promising candidate against the metastasis of human osteosarcoma., (Copyright © 2019. Published by Elsevier B.V.)
- Published
- 2019
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