Open Access

Intermittent hypoxia alleviates increased VEGF and pro‑angiogenic potential in liver cancer cells

  • Authors:
    • Gang Dong
    • Xia‑Hui Lin
    • Hua‑Hua Liu
    • Dong‑Mei Gao
    • Jie‑Feng Cui
    • Zheng‑Gang Ren
    • Rong‑Xin Chen
  • View Affiliations

  • Published online on: June 18, 2019     https://doi.org/10.3892/ol.2019.10486
  • Pages: 1831-1839
  • Copyright: © Dong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Vascular endothelial growth factor (VEGF) is an important angiogenic factor. The VEGF rebound induced by hypoxia following transarterial embolization/chemoembolization for primary liver cancer is associated with treatment failure and poor survival rates in patients. The present study investigated the ability of intermittent hypoxia to alleviate the acute hypoxia‑induced increase of VEGF and decrease the pro‑angiogenic potential of liver cancer cells. The liver cancer cells were exposed to normoxia, or acute or intermittent hypoxia, and the expression of VEGF was determined using reverse transcription‑quantitative polymerase chain reaction analysis and western blotting. The pro‑angiogenic effects of acute or intermittent hypoxia‑exposed liver cancer cells on endothelial cells were assessed in vitro and in vivo. The expression of VEGF in the liver cancer cells exposed to intermittent hypoxia was significantly lower than that in cells exposed to acute hypoxia. Compared with conditioned medium (CM) from acute hypoxia‑exposed liver cancer cells, the CM from intermittent hypoxia‑exposed liver cancer cells showed markedly less promotion of proliferation and tube formation in endothelial cells. Activation of the reactive oxygen species (ROS)/NF‑κB/hypoxia‑inducible factor‑1α/VEGF signaling pathway was increased in the liver cancer cells exposed to acute hypoxia. Exposure to ROS scavenger N‑acetyl‑cysteine or NF‑κB inhibitor PDTC inhibited the activation of the above pathway and the expression of VEGF induced by acute hypoxia. The in vivo pro‑angiogenic effects of intermittent hypoxia‑exposed liver cancer cells on endothelial cells were significantly reduced compared with those of acute hypoxia‑exposed liver cancer cells. Intermittent hypoxia may alleviate the acute hypoxia‑induced increase of VEGF and decrease the pro‑angiogenic potential of liver cancer cells, suggesting a novel treatment strategy.
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August-2019
Volume 18 Issue 2

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

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Copy and paste a formatted citation
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Spandidos Publications style
Dong G, Lin XH, Liu HH, Gao DM, Cui JF, Ren ZG and Chen RX: Intermittent hypoxia alleviates increased VEGF and pro‑angiogenic potential in liver cancer cells. Oncol Lett 18: 1831-1839, 2019
APA
Dong, G., Lin, X., Liu, H., Gao, D., Cui, J., Ren, Z., & Chen, R. (2019). Intermittent hypoxia alleviates increased VEGF and pro‑angiogenic potential in liver cancer cells. Oncology Letters, 18, 1831-1839. https://doi.org/10.3892/ol.2019.10486
MLA
Dong, G., Lin, X., Liu, H., Gao, D., Cui, J., Ren, Z., Chen, R."Intermittent hypoxia alleviates increased VEGF and pro‑angiogenic potential in liver cancer cells". Oncology Letters 18.2 (2019): 1831-1839.
Chicago
Dong, G., Lin, X., Liu, H., Gao, D., Cui, J., Ren, Z., Chen, R."Intermittent hypoxia alleviates increased VEGF and pro‑angiogenic potential in liver cancer cells". Oncology Letters 18, no. 2 (2019): 1831-1839. https://doi.org/10.3892/ol.2019.10486