Triptolide inhibits vascular endothelial growth factor‑mediated angiogenesis in human breast cancer cells

Liu,Huantao; Tang,Lubing; Li,Xiaoyan; Li,Huiying

doi:10.3892/etm.2018.6200

Triptolide inhibits vascular endothelial growth factor‑mediated angiogenesis in human breast cancer cells

Authors:
- Huantao Liu
- Lubing Tang
- Xiaoyan Li
- Huiying Li
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Affiliations: Department of Breast Surgery, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China, Department of Breast Surgery, Ningbo Women and Children's Hospital, Ningbo, Zhejiang 315012, P.R. China, Department of Anesthesiology, The Second Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
Published online on: May 21, 2018 https://doi.org/10.3892/etm.2018.6200
Pages: 830-836
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Triptolide has been demonstrated to induce tumor cell apoptosis. However, the role of triptolide in breast cancer angiogenesis remains unclear. The present study aimed to investigate the function of triptolide in breast cancer and the molecular mechanisms underlying this. The results revealed that triptolide could significantly decrease the expression of vascular endothelial growth factor A (VEGFA) in Hs578T and MDAMB231 breast cancer cells. Furthermore, human umbilical vein endothelial cells were used to perform tube formation and bromodeoxyuridine incorporation assays, which demonstrated an antiangiogenic effect of triptolide. In addition, the effect of triptolide in vivo was examined in a xenograft mouse model, which determined that VEGFA, cluster of differentiation 31 and anti‑proliferation marker protein Ki67 expression in tumor sections was decreased in the triptolide treatment group compared with the control group. Western bolt analysis was performed to investigate the phosphorylation of extracellular signal‑related kinase (ERK)1/2 and RAC‑α serine/threonine‑protein kinase after triptolide treatment, and it's effect on hypoxia inducible factor (HIF)1‑α expression. The results demonstrated that triptolide suppressed ERK1/2 activation and HIF1‑α expression. Furthermore, overexpression of HIF1‑α could partially abrogate the inhibitory effect of triptolide on VEGFA expression. These results suggest that triptolide inhibits breast cancer cell angiogenesis in vitro and in vivo through inhibiting the ERK1/2‑HIF1‑α‑VEGFA axis.

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