Open Access

Combining radiation with autophagy inhibition enhances suppression of tumor growth and angiogenesis in esophageal cancer

  • Authors:
    • Yongshun Chen
    • Xiaohong Li
    • Leiming Guo
    • Xiaoyuan Wu
    • Chunyu He
    • Song Zhang
    • Yanjing Xiao
    • Yuanyuan Yang
    • Daxuan Hao
  • View Affiliations

  • Published online on: April 16, 2015     https://doi.org/10.3892/mmr.2015.3623
  • Pages: 1645-1652
  • Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Radiotherapy is an effective treatment for esophageal cancer; however, tumor resistance to radiation remains a major biological problem. The present study aimed to investigate whether inhibition of autophagy may decrease overall tumor resistance to radiation. The effects of the autophagy inhibitor 3‑methyladenine (3‑MA) on radiosensitivity were tested in the EC9706 human esophageal squamous cell carcinoma cell line by colony formation assay. Furthermore, the synergistic cytotoxic effects of 3‑MA and radiation were assessed in a tumor xenograft model in nude mice. Mechanistic studies were performed using flow cytometry, immunohistochemistry and western blot analysis. The results of the present study demonstrated that radiation induced an accumulation of autophagosomes and 3‑MA effectively inhibited radiation‑induced autophagy. Inhibition of autophagy was shown to significantly increase the radiosensitivity of the tumors in vitro and in vivo. The enhancement ratio of sensitization in EC9706 cells was 1.76 when the cells were treated with 10 mM 3‑MA, alongside ionizing radiation. In addition, autophagy inhibition increased apoptosis and reduced tumor cell proliferation. The combination of radiation and autophagy inhibition resulted in a significant reduction in tumor volume and vasculature in the murine model. The present study demonstrated in vitro and in vivo that radiation‑induced autophagy has a protective effect against cell death, and inhibition of autophagy is able to enhance the radiosensitivity of esophageal squamous cell carcinoma.
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August-2015
Volume 12 Issue 2

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Chen Y, Li X, Guo L, Wu X, He C, Zhang S, Xiao Y, Yang Y and Hao D: Combining radiation with autophagy inhibition enhances suppression of tumor growth and angiogenesis in esophageal cancer. Mol Med Rep 12: 1645-1652, 2015
APA
Chen, Y., Li, X., Guo, L., Wu, X., He, C., Zhang, S. ... Hao, D. (2015). Combining radiation with autophagy inhibition enhances suppression of tumor growth and angiogenesis in esophageal cancer. Molecular Medicine Reports, 12, 1645-1652. https://doi.org/10.3892/mmr.2015.3623
MLA
Chen, Y., Li, X., Guo, L., Wu, X., He, C., Zhang, S., Xiao, Y., Yang, Y., Hao, D."Combining radiation with autophagy inhibition enhances suppression of tumor growth and angiogenesis in esophageal cancer". Molecular Medicine Reports 12.2 (2015): 1645-1652.
Chicago
Chen, Y., Li, X., Guo, L., Wu, X., He, C., Zhang, S., Xiao, Y., Yang, Y., Hao, D."Combining radiation with autophagy inhibition enhances suppression of tumor growth and angiogenesis in esophageal cancer". Molecular Medicine Reports 12, no. 2 (2015): 1645-1652. https://doi.org/10.3892/mmr.2015.3623