Knockdown of ZEB1 suppressed the formation of vasculogenic mimicry and epithelial-mesenchymal transition in the human breast cancer cell line MDA-MB-231

Liang,Weili; Song,Shasha; Xu,Yintao; Li,Huiying; Liu,Huantao

doi:10.3892/mmr.2018.8677

Knockdown of ZEB1 suppressed the formation of vasculogenic mimicry and epithelial-mesenchymal transition in the human breast cancer cell line MDA-MB-231

Authors:
- Weili Liang
- Shasha Song
- Yintao Xu
- Huiying Li
- Huantao Liu
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Affiliations: Department of Breast Surgery, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China, Department of Pathology, Jinan Central Hospital, Jinan, Shandong 250013, P.R. China, Department of Gynecology and Obstetrics, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China, Department of Anesthesiology, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China
Published online on: March 5, 2018 https://doi.org/10.3892/mmr.2018.8677
Pages: 6711-6716

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Abstract

Breast cancer is a common malignant tumor in women. It has been suggested that a type of microcirculation pattern that does not rely on host microvascular endothelial cells known as vasculogenic mimicry (VM) may contribute to the poor effect of anti‑angiogenesis treatment on some patients with breast cancer. However, the formation and regulatory mechanism of VM in breast cancer are unclear and still require further investigation. The present study examined whether decreasing the expression of zinc finger E‑box binding homeobox (ZEB1) using siRNA can inhibit the formation of VM in Triple Negative Breast Cancer (TNBC), and its specific function and molecular mechanism. mRNA and protein expression were detected by RT‑qPCR and western blotting. Invasion assay and tube formation assay were also performed. The results demonstrated that ZEB1 small hairpin (sh)RNA inhibited the formation of VM. Knockdown of ZEB1 markedly inhibited the expression of vimentin in MDA‑MB‑231 cells and markedly increased the expression of E‑cadherin. It was suggested that ZEB1 shRNA may have inhibited the epithelial‑mesenchymal transition (EMT). In addition, ZEB1 shRNA inhibited the invasion of MDA‑MB‑231 cells and suppressed the expression of fetal liver kinase 1 (flk‑1). The flk‑1 inhibitor Semaxanib inhibited the formation of VM; thus, ZEB1 shRNA inhibited EMT and cell invasion, and may have inhibited the formation of VM through flk‑1. The present study contributed further understanding on the theory of tumor angiogenesis and provided theoretical basis for novel targeted therapy of TNBC.

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