Open Access

CRISPR/Cas9‑mediated hypoxia inducible factor‑1α knockout enhances the antitumor effect of transarterial embolization in hepatocellular carcinoma

  • Authors:
    • Quan Liu
    • Dahua Fan
    • Dickson Adah
    • Zhengzhi Wu
    • Renyan Liu
    • Qiao‑Ting Yan
    • Yue Zhang
    • Zhi‑Yong Du
    • Dou Wang
    • Yan Li
    • Shi‑Yun Bao
    • Li‑Ping Liu
  • View Affiliations

  • Published online on: August 23, 2018     https://doi.org/10.3892/or.2018.6667
  • Pages: 2547-2557
  • Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Transarterial embolization (TAE) is a palliative option commonly used for the treatment of advanced, unresectable hepatocellular carcinoma (HCC). However, patient prognosis in regards to overall survival has not improved with this method, mainly due to hypoxia‑inducible factor‑1α (HIF‑1α)‑induced angiogenesis and invasiveness. Thus, it is hypothesized that HIF‑1α may be an ideal knockout target for the treatment of HCC in combination with TAE. Thus, in the present study, HIF‑1α knockout was conducted in human liver cancer SMMC‑7721 cells and a xenograft HCC model was established using a lentivirus‑mediated CRISPR/Cas system (LV‑Cas) with small guide RNA‑721 (LV‑H721). Furthermore, hepatic artery ligation (HAL) was used to mimic human transarterial chemoembolization in mice. The results revealed that HIF‑1α was highly expressed in both HCC patient tissues and SMMC‑7721‑induced tumor tissues. The HIF‑1α knockout in SMMC‑7721 cells significantly suppressed cell invasiveness and migration, and induced cell apoptosis under CoCl2‑mimicking hypoxic conditions. Compared with the control groups, HAL + LV‑H721 inhibited SMMC‑7721 tumor growth in orthotopic HCC and markedly prolonged the survival of HCC‑bearing mice, which was accompanied by a lower CD31 expression (tumor angiogenesis) and increased apoptosis in the tumor cells. These findings demonstrated a valuable antitumor synergism in combining CRISPR/Cas9‑mediated HIF‑1α knockout with TAE in mice and highlighted the possibility that HIF‑1α may be an effective therapeutic knockout target in combination with TAE for HCC treatment.
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November-2018
Volume 40 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Copy and paste a formatted citation
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Spandidos Publications style
Liu Q, Fan D, Adah D, Wu Z, Liu R, Yan QT, Zhang Y, Du ZY, Wang D, Li Y, Li Y, et al: CRISPR/Cas9‑mediated hypoxia inducible factor‑1α knockout enhances the antitumor effect of transarterial embolization in hepatocellular carcinoma. Oncol Rep 40: 2547-2557, 2018
APA
Liu, Q., Fan, D., Adah, D., Wu, Z., Liu, R., Yan, Q. ... Liu, L. (2018). CRISPR/Cas9‑mediated hypoxia inducible factor‑1α knockout enhances the antitumor effect of transarterial embolization in hepatocellular carcinoma. Oncology Reports, 40, 2547-2557. https://doi.org/10.3892/or.2018.6667
MLA
Liu, Q., Fan, D., Adah, D., Wu, Z., Liu, R., Yan, Q., Zhang, Y., Du, Z., Wang, D., Li, Y., Bao, S., Liu, L."CRISPR/Cas9‑mediated hypoxia inducible factor‑1α knockout enhances the antitumor effect of transarterial embolization in hepatocellular carcinoma". Oncology Reports 40.5 (2018): 2547-2557.
Chicago
Liu, Q., Fan, D., Adah, D., Wu, Z., Liu, R., Yan, Q., Zhang, Y., Du, Z., Wang, D., Li, Y., Bao, S., Liu, L."CRISPR/Cas9‑mediated hypoxia inducible factor‑1α knockout enhances the antitumor effect of transarterial embolization in hepatocellular carcinoma". Oncology Reports 40, no. 5 (2018): 2547-2557. https://doi.org/10.3892/or.2018.6667