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Tumor Biology

, Volume 37, Issue 4, pp 4679–4688 | Cite as

Endostatin combined with radiotherapy suppresses vasculogenic mimicry formation through inhibition of epithelial–mesenchymal transition in esophageal cancer

  • Xiaochen Chen
  • Hao Zhang
  • Hongcheng Zhu
  • Xi Yang
  • Yuehua Yang
  • Yan Yang
  • Hua Min
  • Guangzong Chen
  • Jia Liu
  • Jing Lu
  • Hongyan Cheng
  • Xinchen Sun
Original Article

Abstract

The growth of solid tumors requires angiogenesis to provide oxygen and nutrients and to support cell proliferation. The switch from an avascular to a vascular phenotype is typically related to acceleration of tumor growth. Anti-angiogenic therapy is becoming a very promising way for malignant tumors. Meanwhile, malignant tumor cells themselves were able to develop the formation of cell-lined vessels that contribute to tumor neovascularization and supply the nutrients and oxygen, which is called vasculogenic mimicry (VM). However, the molecular mechanism of VM remains unclear. The purpose of this study was to investigate the efficacy of the novel recombinant human endostatin (rh-Endo) protein combined with radiotherapy on human esophageal squamous cell carcinoma (ESCC) cell lines Eca-109 and TE13. Our results showed that rh-Endo combined with radiotherapy significantly inhibited the proliferation, migration, invasion, and VM of human esophageal cancer cells in a dose-dependent manner; however, it has no direct effect on apoptosis of carcinoma cells, which indicated that rh-Endo combined with radiotherapy significantly changed the microenvironment of esophageal carcinoma, and played an important role in preventing distant metastasis. Our findings suggested that rh-Endo inhibited the metastasis of esophageal cancer and the activation of AKT pathway, and the down-regulation of epithelial–mesenchymal transition (EMT) may be associated with such effect of rh-Endo. These results also supported the bright prospect of rh-Endo combined with radiotherapy for clinical applications in the future.

Keywords

Recombinant human endostatin Vasculogenic mimicry Radiotherapy Esophageal carcinoma Epithelial–mesenchymal transition 

Abbreviation

ESCC

Esophageal squamous cell carcinoma

RT

Radiotherapy

rh-Endo

Recombinant human endostatin

NSCLC

Non-small-cell lung cancer

EMT

Epithelial–mesenchymal transition

VM

Vaculogenic mimicry

DMSO

Dimethyl sulfoxide

DMEM

Dulbecco’s modified eagle medium

FITC

Fluorescein isothiocyanate

CCk-8

Cell counting kit-8

PTEN

Phosphatase and tensin homolog deleted on chromosome ten

Akt

Protein kinase B PKB

GSK-3β

Glycogen synthase kinase 3β

GAPDH

Glyceraldehyde-3-phosphate dehydrogenase

Notes

Acknowledgments

This work was supported by the Natural Science Foundation of China (No. 81272504, No. 81472809), Innovation Team [No. LJ201123 (EH11)], A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) (JX10231801), grants from Key Academic Discipline of Jiangsu Province “Medical Aspects of Specific Environments”, Research and Innovation Project for College Graduates of Jiangsu Province (KYLX_0955). The methods were carried out in accordance with the approved guidelines.

Compliance with Ethical Standards

Conflicts of interest

The authors declare that they have no conflicts of interest.

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Xiaochen Chen
    • 1
  • Hao Zhang
    • 1
  • Hongcheng Zhu
    • 1
  • Xi Yang
    • 1
  • Yuehua Yang
    • 1
  • Yan Yang
    • 1
  • Hua Min
    • 1
  • Guangzong Chen
    • 1
  • Jia Liu
    • 1
  • Jing Lu
    • 1
  • Hongyan Cheng
    • 2
  • Xinchen Sun
    • 1
  1. 1.Department of Radiation OncologyThe First Affiliated Hospital of Nanjing Medical UniversityNanjingChina
  2. 2.Department of General Internal MedicineThe First Affiliated Hospital of Nanjing Medical UniversityNanjingChina

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