期刊
CHEMICO-BIOLOGICAL INTERACTIONS
卷 307, 期 -, 页码 158-166出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.cbi.2019.05.005
关键词
Glaucocalyxin A; Osteosarcoma; Epithelial-mesenchymal transition (EMT); Transforming growth factor-beta 1 (TGF-beta 1); Smad
资金
- National Natural Science Foundation of China [81703556]
- Natural Science Foundation of Jiangsu Province [BK20171024]
- Jiangsu Synergetic Innovation Center for Advanced Bio-Manufacture [XTD1819]
- Key University Science Research Project of Jiangsu Province [15KJA430006]
- National Key Special Project of Science and Technology for Innovation Drugs of China [2017ZX09301-013]
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-beta 1 (TGF-beta 1)-induced migration, invasion and EMT of low-metastatic osteosarcoma U2OS cells. Glaucocalyxin A inhibited TGF-beta-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-beta 1-induced EMT by inhibiting TGF-beta 1/Smad2/3 signaling pathway in osteosarcoma. Therefore, Glaucocalyxin A might be a promising candidate against the metastasis of human osteosarcoma.
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