Open Access

Inhibiting TrxR suppresses liver cancer by inducing apoptosis and eliciting potent antitumor immunity

  • Authors:
    • Hong Lei
    • Guan Wang
    • Jian Zhang
    • Qiuju Han
  • View Affiliations

  • Published online on: September 27, 2018     https://doi.org/10.3892/or.2018.6740
  • Pages: 3447-3457
  • Copyright: © Lei et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Liver cancer is one of the most common malignant tumors worldwide. Thioredoxin reductase (TrxR) is highly expressed in liver cancer cells. The present study aimed to investigate the effect of inhibiting TrxR on liver cancer and to better understand the underlying molecular and immuno­logical mechanisms associated with inhibition. It was demonstrated that targeting TrxR inhibited the growth and induced apoptosis of liver cancer cells, which was accompanied by activation of the mitogen associated protein kinase pathway. This inhibition was dependent on the production of reactive oxygen species (ROS). Blockage of ROS production reversed TrxR inhibitor‑induced antitumor effects. Blocking the Trx/TrxR system activated the mammalian target of rapamycin pathway and inhibited autophagy, which occurred in a ROS‑independent manner. TrxR inhibition led to lesions in the mitochondrial membrane, indicated by alterations in membrane potential. Mouse xenograft experiments were highly consistent with in vitro studies. Most importantly, blocking the Trx/TrxR system improved the tumor immune microenvironment. Together, these data demonstrated that TrxR is a potential target for liver cancer therapy, which could inhibit hepatocarcinogenesis and progression, and improve the antitumor immune response.
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December-2018
Volume 40 Issue 6

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
Lei H, Wang G, Zhang J and Han Q: Inhibiting TrxR suppresses liver cancer by inducing apoptosis and eliciting potent antitumor immunity . Oncol Rep 40: 3447-3457, 2018
APA
Lei, H., Wang, G., Zhang, J., & Han, Q. (2018). Inhibiting TrxR suppresses liver cancer by inducing apoptosis and eliciting potent antitumor immunity . Oncology Reports, 40, 3447-3457. https://doi.org/10.3892/or.2018.6740
MLA
Lei, H., Wang, G., Zhang, J., Han, Q."Inhibiting TrxR suppresses liver cancer by inducing apoptosis and eliciting potent antitumor immunity ". Oncology Reports 40.6 (2018): 3447-3457.
Chicago
Lei, H., Wang, G., Zhang, J., Han, Q."Inhibiting TrxR suppresses liver cancer by inducing apoptosis and eliciting potent antitumor immunity ". Oncology Reports 40, no. 6 (2018): 3447-3457. https://doi.org/10.3892/or.2018.6740