Open Access

Targeting hypoxia-inducible factor-2α enhances sorafenib antitumor activity via β-catenin/C-Myc-dependent pathways in hepatocellular carcinoma

  • Authors:
    • Feng Liu
    • Xiaofeng Dong
    • Hong Lv
    • Peng Xiu
    • Tao Li
    • Fuhai Wang
    • Zongzhen Xu
    • Jie Li
  • View Affiliations

  • Published online on: June 3, 2015     https://doi.org/10.3892/ol.2015.3315
  • Pages: 778-784
  • Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Sorafenib is a type of multikinase inhibitor that exhibits antiangiogenic and antiproliferative effects; in addition, sorafenib is a unique first‑line drug recommended for the treatment of advanced hepatocellular carcinoma (HCC). However, the effectiveness of HCC treatment remains poor due to acquired drug resistance. It has been suggested that hypoxia, induced as a results of the antiangiogenic effects of sustained sorafenib treatment, may be an important factor in sorafenib resistance. The transcription factor hypoxia‑inducible factor (HIF)‑2α has been reported to be associated with cell proliferation under hypoxic conditions; therefore, it was hypothesized that hypoxia may enhance tumor cell proliferation via this mechanism. The present study aimed to evaluate whether the knock‑down of HIF‑2α was able to enhance the therapeutic efficacy of sorafenib in order to effectively treat HCC. The results demonstrated that hypoxia protected HCC cells against sorafenib; however, short hairpin RNA‑HIF‑2α transfection in combination with sorafenib treatment exhibited a significantly synergistic effect against HCC cell proliferation. In addition, HCC cells acquired increased β‑catenin/C‑Myc expression, which enhanced proliferation under hypoxic conditions; however, targeted knock‑down of HIF‑2α or C‑Myc markedly decreased cell proliferation in HCC cells. In conclusion, the results of the present study indicated that the targeted knock‑down of HIF‑2α in combination with sorafenib may be a promising strategy for the treatment of HCC.
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August-2015
Volume 10 Issue 2

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Liu F, Dong X, Lv H, Xiu P, Li T, Wang F, Xu Z and Li J: Targeting hypoxia-inducible factor-2α enhances sorafenib antitumor activity via β-catenin/C-Myc-dependent pathways in hepatocellular carcinoma. Oncol Lett 10: 778-784, 2015
APA
Liu, F., Dong, X., Lv, H., Xiu, P., Li, T., Wang, F. ... Li, J. (2015). Targeting hypoxia-inducible factor-2α enhances sorafenib antitumor activity via β-catenin/C-Myc-dependent pathways in hepatocellular carcinoma. Oncology Letters, 10, 778-784. https://doi.org/10.3892/ol.2015.3315
MLA
Liu, F., Dong, X., Lv, H., Xiu, P., Li, T., Wang, F., Xu, Z., Li, J."Targeting hypoxia-inducible factor-2α enhances sorafenib antitumor activity via β-catenin/C-Myc-dependent pathways in hepatocellular carcinoma". Oncology Letters 10.2 (2015): 778-784.
Chicago
Liu, F., Dong, X., Lv, H., Xiu, P., Li, T., Wang, F., Xu, Z., Li, J."Targeting hypoxia-inducible factor-2α enhances sorafenib antitumor activity via β-catenin/C-Myc-dependent pathways in hepatocellular carcinoma". Oncology Letters 10, no. 2 (2015): 778-784. https://doi.org/10.3892/ol.2015.3315