期刊
ONCOLOGY LETTERS
卷 16, 期 2, 页码 2289-2298出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/ol.2018.8943
关键词
oridonin; epithelial-mesenchymal transition; angiogenesis; metastasis; breast cancer
类别
资金
- Natural Science Foundation of Tianjin Medical University [2015KYZQ13]
- Postdoctoral Science Foundation of China [2016M591398]
- Basic Scientific Research Fund of Tianjin Municipal Education Commission [2016YD07]
Metastasis is the primary cause of mortality in patients with breast cancer and lacks effective therapeutic agents. Oridonin, an active diterpenoid compound isolated from Rabdosia rubescens, was identified to be the most potent anti-tumor ingredient. However, the molecular mechanisms responsible for its anti-metastatic effects remain unclear. In the present study, oridonin significantly suppressed the migration, invasion and adhesion of MDA-MB-231 and 4T1 breast cancer cells, and inhibited tube formation of human umbilical vein endothelial cells in a dose-dependent manner. The expression levels of epithelial-mesenchymal transition (EMT)-associated marker and the hypoxia inducible factor 1 alpha (HIF-1 alpha)/vascular endothelium growth factor (VEGF) signaling pathway mRNA and proteins were determined by reverse transcription-quantitative polymerase chain reaction and western blotting, respectively in vitro. The results demonstrated that oridonin effectively inhibited EMT as demonstrated by the significant increases in the expression levels of E-cadherin, and decreased expression of N-cadherin, Vimentin and Snail. In addition, oridonin exerted its anti-angiogenesis activity through significantly decreasing HIF-1 alpha, VEGF-A and VEGF receptor-2 protein expression. Furthermore, oridonin was demonstrated to decrease the micro-vessel density as evidenced by the decreased expression of cluster of differentiation 31, a marker for neovasculature. In brief, oridonin inhibits tumor cell migration, invasion and adhesion, as well as tumor angiogenesis, which are mediated by suppressing EMT and the HIF1 alpha/VEGF signaling pathway. The results of the present study suggest that oridonin may be a promising anti-metastatic agent in breast cancer treatment.
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