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Inhibition of Glut1 by WZB117 sensitizes radioresistant breast cancer cells to irradiation

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Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

Breast cancer is the most common type of cancer with high incidence in women. Currently, identifying new therapies that selectively inhibit tumor growth without damaging normal tissue are a major challenge of cancer research. One of the features of cancer cells is that they do not consume more oxygen even under normal oxygen circumstances but prefer to aerobic glycolysis through the enhanced catabolism of glucose and glutamine. In this study, we investigate the mechanisms of the radioresistance in breast cancer cells.

Methods

Human breast cancer cells MDA-MB-231 and MCF-7 were treated with radiation alone, Glut1 inhibitor alone or the combination of both to evaluate cell glucose metabolism and apoptosis. By the establishment of radioresistant cell line, we investigate the mechanisms of the combined treatments of radiation with Glut1 inhibitor in the radioresistant cells.

Results

The glucose metabolism and the expression of Glut1 are significantly stimulated by radiotherapy. We report the radioresistant breast cancer cells exhibit upregulated Glut1 expression and glucose metabolism. In addition, we observed overexpression of Glut1 renders breast cancer cells resistant to radiation and knocking down of Glut1 sensitizes breast cancer cells to radiation. We treated breast cancer cells with radiation and WZB117 which inhibits Glut1 expression and glucose metabolism and found the combination of WZB117 and radiation exhibits synergistically inhibitory effects on breast cancer cells. Finally, we demonstrate the inhibition of Glut1 re-sensitizes the radioresistant cancer cells to radiation.

Conclusions

This study reveals the roles of Glut1 in the radiosensitivity of human breast cancer. It will provide new mechanisms and strategies for the sensitization of cancer cells to radiotherapy through regulation of glucose metabolism.

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Acknowledgments

The authors thank all the staff and faculty working in Breast Disease Center, Southwest Hospital, Third Military Medical University, Chongqing, China. We thank Dr. Yan Zhou for providing the editorial assistance and Dr. Jia Ming for critical review of the manuscript.

Author contributions

FZH. and L.J.F. designed research; F.ZH., J.M. and L.J.F. developed methodology; F.ZH., J.M. and Y.ZH. performed experiments and acquisition of data; F.ZH., J.M., Y.ZH. and L.J.F analyzed data and F.ZH., J.M. and L.J.F. wrote the paper

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Authors and Affiliations

  1. Department of Recuperation, NO. 281 Hospital of PLA, Qinhuangdao, 066100, China

    Fei Zhao

  2. Breast Disease Center, Southwest Hospital, Third Military Medical University, NO. 29 Gaotanyan Street, Chongqing, 400038, China

    Jia Ming, Yan Zhou & Linjun Fan

Authors
  1. Fei Zhao
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  2. Jia Ming
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  3. Yan Zhou
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Corresponding author

Correspondence to Linjun Fan.

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Zhao, F., Ming, J., Zhou, Y. et al. Inhibition of Glut1 by WZB117 sensitizes radioresistant breast cancer cells to irradiation. Cancer Chemother Pharmacol 77, 963–972 (2016). https://doi.org/10.1007/s00280-016-3007-9

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  • DOI: https://doi.org/10.1007/s00280-016-3007-9

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