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

  • Original Article
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Tumor Biology

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.

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Abbreviations

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

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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.

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    Authors and Affiliations

    1. Department of Radiation Oncology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China

      Xiaochen Chen, Hao Zhang, Hongcheng Zhu, Xi Yang, Yuehua Yang, Yan Yang, Hua Min, Guangzong Chen, Jia Liu, Jing Lu & Xinchen Sun

    2. Department of General Internal Medicine, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China

      Hongyan Cheng

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    1. Xiaochen Chen
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    Xiaochen Chen, Hao Zhang and Hongcheng Zhu contributed equally to this work.

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    Chen, X., Zhang, H., Zhu, H. et al. Endostatin combined with radiotherapy suppresses vasculogenic mimicry formation through inhibition of epithelial–mesenchymal transition in esophageal cancer. Tumor Biol. 37, 4679–4688 (2016). https://doi.org/10.1007/s13277-015-4284-3

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    • DOI: https://doi.org/10.1007/s13277-015-4284-3

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