Open Access

Targeting hexokinase 2 inhibition promotes radiosensitization in HPV16 E7-induced cervical cancer and suppresses tumor growth

  • Authors:
    • Yuan Liu
    • Tracy Murray-Stewart
    • Robert A. Casero
    • Ioannis Kagiampakis
    • Lihua Jin
    • Jiawen Zhang
    • Huihui Wang
    • Qi Che
    • Huan Tong
    • Jieqi Ke
    • Feizhou Jiang
    • Fangyuan Wang
    • Xiaoping Wan
  • View Affiliations

  • Published online on: May 2, 2017     https://doi.org/10.3892/ijo.2017.3979
  • Pages: 2011-2023
  • Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

In order to improve the sensitivity of cervical cancer cells to irradiation therapy, we targeted hexokinase 2 (HK2), the first rate-limiting enzyme of glycolysis, and explore its role in cervical cancer cells. We suppressed HK2 expression and/or function by shRNA and/or metformin and found HK2 inhibition enhanced cells apoptosis with accelerating expression of cleaved PARP and caspase-3. HK2 inhibition also induced much inferior proliferation of cervical cancer cells both in vitro and in vivo with diminishing expression of mTOR, MIB and MGMT. Moreover, HK2 inhibition altered the metabolic profile of cervical cancer cells to one less dependent on glycolysis with a reinforcement of mitochondrial function and an ablation of lactification ability. Importantly, cervical cancer cells contained HK2 inhibition displayed more sensitivity to irradiation. Further results indicated that HPV16 E7 oncoprotein altered the glucose homeostasis of cervical cancer cells into glycolysis by coordinately promoting HK2 expression and its downregulation of glycolysis. Taken together, our findings supported a mechanism whereby targeting HK2 inhibition contributed to suppress HPV16 E7-induced tumor glycolysis metabolism phenotype, inhibiting tumor growth, and induced apoptosis, blocking the cancer cell energy sources and ultimately enhanced the sensitivity of HPV(+) cervical cancer cells to irradiation therapy.
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June-2017
Volume 50 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Liu Y, Murray-Stewart T, Casero RA, Kagiampakis I, Jin L, Zhang J, Wang H, Che Q, Tong H, Ke J, Ke J, et al: Targeting hexokinase 2 inhibition promotes radiosensitization in HPV16 E7-induced cervical cancer and suppresses tumor growth. Int J Oncol 50: 2011-2023, 2017
APA
Liu, Y., Murray-Stewart, T., Casero, R.A., Kagiampakis, I., Jin, L., Zhang, J. ... Wan, X. (2017). Targeting hexokinase 2 inhibition promotes radiosensitization in HPV16 E7-induced cervical cancer and suppresses tumor growth. International Journal of Oncology, 50, 2011-2023. https://doi.org/10.3892/ijo.2017.3979
MLA
Liu, Y., Murray-Stewart, T., Casero, R. A., Kagiampakis, I., Jin, L., Zhang, J., Wang, H., Che, Q., Tong, H., Ke, J., Jiang, F., Wang, F., Wan, X."Targeting hexokinase 2 inhibition promotes radiosensitization in HPV16 E7-induced cervical cancer and suppresses tumor growth". International Journal of Oncology 50.6 (2017): 2011-2023.
Chicago
Liu, Y., Murray-Stewart, T., Casero, R. A., Kagiampakis, I., Jin, L., Zhang, J., Wang, H., Che, Q., Tong, H., Ke, J., Jiang, F., Wang, F., Wan, X."Targeting hexokinase 2 inhibition promotes radiosensitization in HPV16 E7-induced cervical cancer and suppresses tumor growth". International Journal of Oncology 50, no. 6 (2017): 2011-2023. https://doi.org/10.3892/ijo.2017.3979