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Fenofibrate enhances radiosensitivity of esophageal squamous cell carcinoma by suppressing hypoxia-inducible factor-1α expression

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Tumor Biology

Abstract

Radiation therapy is widely used in esophageal squamous cell carcinoma (ESCC). Promoting radiation sensitivity is important. Recent studies have shown that fenofibrate can inhibit the growth of several cancer lines and hypoxia-inducible factor-1α (HIF-1α) expression in MCF-7 cells. However, few studies on the radiosensitive effect of fenofibrate on ESCCs under hypoxic condition have been conducted. In this study, we assessed the radiosensitive effects of fenofibrate on human ESCC cells. In vitro experiments showed the inhibition of cytotoxic effects after ionizing irradiation. We measured cell viability and clonogenic survival rate. Flow cytometry showed that fenofibrate pretreatment promoted apoptosis. The in vivo data also suggest that fenofibrate had radiosensitizing effects in ECA-109 cells xenografted into nude mice. Western blot and immunohistochemical analyses revealed that the HIF-1α and vascular endothelial growth factor (VEGF) protein content decreased by fenofibrate. Thus, the inhibition of HIF-1α and VEGF expression in ESCC cells contributed to the radiosensitive effect. These data suggest that fenofibrate may be a potential radiosensitive drug.

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Acknowledgments

This work was supported by 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.”

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Authors and Affiliations

  1. Department of Radiation Oncology, Nantong Tumor Hospital, Nantong University, Nantong, China

    Yangyang Ge, Baixia Yang, Kuiling Zhao, Zhijun Wu, Guojian Cheng, Feng Wang, Feng Ni, Qin Ge, Yanguang Yang, Guomei Tai & Jing Cai

  2. Department of Radiation Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

    Jia Liu, Xi Yang, Hongcheng Zhu & Xinchen Sun

Authors
  1. Yangyang Ge
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  2. Jia Liu
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  3. Xi Yang
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  4. Hongcheng Zhu
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  5. Baixia Yang
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  6. Kuiling Zhao
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  7. Zhijun Wu
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  8. Guojian Cheng
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  9. Feng Wang
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  10. Feng Ni
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  11. Qin Ge
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  12. Yanguang Yang
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  13. Guomei Tai
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  14. Xinchen Sun
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  15. Jing Cai
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Corresponding author

Correspondence to Jing Cai.

Additional information

Yangyang Ge, Jia Liu, and Xi Yang contributed equally to this study.

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Ge, Y., Liu, J., Yang, X. et al. Fenofibrate enhances radiosensitivity of esophageal squamous cell carcinoma by suppressing hypoxia-inducible factor-1α expression. Tumor Biol. 35, 10765–10771 (2014). https://doi.org/10.1007/s13277-014-2149-9

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  • DOI: https://doi.org/10.1007/s13277-014-2149-9

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