Oridonin inhibits VEGF‑A‑associated angiogenesis and epithelial‑mesenchymal transition of breast cancer in vitro and in vivo

Li,Chunyu; Wang,Qi; Shen,Shen; Wei,Xiaolu; Li,Guoxia

doi:10.3892/ol.2018.8943

Oridonin inhibits VEGF‑A‑associated angiogenesis and epithelial‑mesenchymal transition of breast cancer in vitro and in vivo

Authors:
- Chunyu Li
- Qi Wang
- Shen Shen
- Xiaolu Wei
- Guoxia Li
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Affiliations: Department of Integrated Chinese Traditional and Western Medicine, International Medical School, Tianjin Medical University, Tianjin 300070, P.R. China, Department of Oncology, Shanghai Pulmonary Hospital Affiliated to Tongji University, Shanghai 200433, P.R. China
Published online on: June 11, 2018 https://doi.org/10.3892/ol.2018.8943
Pages: 2289-2298
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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 1α (HIF‑1α)/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‑1α, 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 HIF‑1α/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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