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Article Open Access

2-Methoxyestradiol enhances radiosensitivity in radioresistant melanoma MDA-MB-435R cells by regulating glycolysis via HIF-1α/PDK1 axis

  • Authors:
    • Hong Zhao
    • Huangang Jiang
    • Zheng Li
    • Yafei Zhuang
    • Yinyin Liu
    • Shuliang Zhou
    • Youde Xiao
    • Conghua Xie
    • Fuxiang Zhou
    • Yunfeng Zhou
  • View Affiliations / Copyright

    Affiliations: Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital of Wuhan University, Wuchang, Wuhan, Hubei 430071, P.R. China, Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuchang, Wuhan, Hubei 430071, P.R. China
    Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1531-1540
    |
    Published online on: March 22, 2017
       https://doi.org/10.3892/ijo.2017.3924
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Abstract

HIF-1α overexpression is associated with radio­resistance of various cancers. A radioresistant human melanoma cell model MDA-MB-435R (435R) was established by us previously. Compared with the parental cells MDA-MB‑435 (435S), an elevated level of HIF-1α expression in 435R cells was demonstrated in our recent experiments. Therefore, in the current study, we sought to determine whether selective HIF-1α inhibitors could radiosensitize the 435R cells to X-ray, and to identify the potential mechanisms. Our data demonstrated that inhibition of HIF-1α with 2-methoxyestradiol (2-MeOE2) significantly enhanced radiosensitivity of 435R cells. 2-MeOE2 increased DNA damage and ratio of apoptosis cells induced by irradiation. Whereas, cell proliferation and the expression of pyruvate dehydrogenase kinase 1 (PDK1) were decreased after 2-MeOE2 treatment. The change of expression of GLUT1, LDHA and the cellular ATP level and extracellular lactate production indicates that 2-MeOE2 suppressed glycolytic state of 435R cells. In addition, the radioresistance, glycolytic state and cell proliferation of 435R cells were also decreased after inhibiting pyruvate dehydrogenase kinase 1 (PDK1) with dichloroacetate (DCA). DCA could also increase DNA damage and ratio of apoptotic cells induced by irradiation. These results also suggest that inhibition of HIF-1α with 2-MeOE2 sensitizes radioresistant melanoma cells 435R to X-ray irradiation through targeting the glycolysis that is regulated by PDK1. Selective inhibitors of HIF-1α and glycolysis are potential drugs to enhance radio­sensitivity of melanoma cells.
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Copy and paste a formatted citation
Spandidos Publications style
Zhao H, Jiang H, Li Z, Zhuang Y, Liu Y, Zhou S, Xiao Y, Xie C, Zhou F, Zhou Y, Zhou Y, et al: 2-Methoxyestradiol enhances radiosensitivity in radioresistant melanoma MDA-MB-435R cells by regulating glycolysis via HIF-1α/PDK1 axis. Int J Oncol 50: 1531-1540, 2017.
APA
Zhao, H., Jiang, H., Li, Z., Zhuang, Y., Liu, Y., Zhou, S. ... Zhou, Y. (2017). 2-Methoxyestradiol enhances radiosensitivity in radioresistant melanoma MDA-MB-435R cells by regulating glycolysis via HIF-1α/PDK1 axis. International Journal of Oncology, 50, 1531-1540. https://doi.org/10.3892/ijo.2017.3924
MLA
Zhao, H., Jiang, H., Li, Z., Zhuang, Y., Liu, Y., Zhou, S., Xiao, Y., Xie, C., Zhou, F., Zhou, Y."2-Methoxyestradiol enhances radiosensitivity in radioresistant melanoma MDA-MB-435R cells by regulating glycolysis via HIF-1α/PDK1 axis". International Journal of Oncology 50.5 (2017): 1531-1540.
Chicago
Zhao, H., Jiang, H., Li, Z., Zhuang, Y., Liu, Y., Zhou, S., Xiao, Y., Xie, C., Zhou, F., Zhou, Y."2-Methoxyestradiol enhances radiosensitivity in radioresistant melanoma MDA-MB-435R cells by regulating glycolysis via HIF-1α/PDK1 axis". International Journal of Oncology 50, no. 5 (2017): 1531-1540. https://doi.org/10.3892/ijo.2017.3924
Copy and paste a formatted citation
x
Spandidos Publications style
Zhao H, Jiang H, Li Z, Zhuang Y, Liu Y, Zhou S, Xiao Y, Xie C, Zhou F, Zhou Y, Zhou Y, et al: 2-Methoxyestradiol enhances radiosensitivity in radioresistant melanoma MDA-MB-435R cells by regulating glycolysis via HIF-1α/PDK1 axis. Int J Oncol 50: 1531-1540, 2017.
APA
Zhao, H., Jiang, H., Li, Z., Zhuang, Y., Liu, Y., Zhou, S. ... Zhou, Y. (2017). 2-Methoxyestradiol enhances radiosensitivity in radioresistant melanoma MDA-MB-435R cells by regulating glycolysis via HIF-1α/PDK1 axis. International Journal of Oncology, 50, 1531-1540. https://doi.org/10.3892/ijo.2017.3924
MLA
Zhao, H., Jiang, H., Li, Z., Zhuang, Y., Liu, Y., Zhou, S., Xiao, Y., Xie, C., Zhou, F., Zhou, Y."2-Methoxyestradiol enhances radiosensitivity in radioresistant melanoma MDA-MB-435R cells by regulating glycolysis via HIF-1α/PDK1 axis". International Journal of Oncology 50.5 (2017): 1531-1540.
Chicago
Zhao, H., Jiang, H., Li, Z., Zhuang, Y., Liu, Y., Zhou, S., Xiao, Y., Xie, C., Zhou, F., Zhou, Y."2-Methoxyestradiol enhances radiosensitivity in radioresistant melanoma MDA-MB-435R cells by regulating glycolysis via HIF-1α/PDK1 axis". International Journal of Oncology 50, no. 5 (2017): 1531-1540. https://doi.org/10.3892/ijo.2017.3924
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