Inhibition of livin overcomes radioresistance in nasopharyngeal carcinoma cells

PLoS One. 2020 Mar 2;15(3):e0229272. doi: 10.1371/journal.pone.0229272. eCollection 2020.

Abstract

Background and aims: Radiotherapy is one of the major remedies for the treatment of cancer, including nasopharyngeal carcinoma (NPC). Radioresistance occurs very often in target cells that is a large drawback in cancer treated with radiotherapy. Livin involves the over-growth of cancer cells. This study aims to investigate the role of livin in the radioresistance formation in NPC cells.

Methods: NPC cell lines were exposed to small doses of irradiation to establish a cell model of radioresistance, in which the role of livin in the development of radioresistance was evaluated.

Results: The expression of livin was observed in NPC cells, which was significantly increased after exposing to small doses of irradiation. A negative correlation was detected between livin and Fas expression in NPC cells. Livin formed a complex with heat shock factor-1 (HSF1, the transcription factor of Fas) in NPC cells after irradiation, which sped up ubiquitination of HSF1. Livin was involved in suppressing Fas expression in NPC cells with radioresistance. Exposure to livin inhibitors prevented radioresistance development and overcame the established radioresistance in NPC cells.

Conclusions: Livin expression in NPC cells plays a critical role in the development of radioresistance. Depletion of livin increases the sensitiveness of NPC cells to irradiation. Target therapy against livin may have the translational potential for the treatment of NPC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / antagonists & inhibitors
  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Proliferation / radiation effects
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / radiation effects
  • Heat Shock Transcription Factors / metabolism
  • Humans
  • Inhibitor of Apoptosis Proteins / antagonists & inhibitors
  • Inhibitor of Apoptosis Proteins / genetics*
  • Inhibitor of Apoptosis Proteins / metabolism*
  • Nasopharyngeal Carcinoma / genetics
  • Nasopharyngeal Carcinoma / metabolism*
  • Nasopharyngeal Carcinoma / radiotherapy
  • Nasopharyngeal Neoplasms / genetics
  • Nasopharyngeal Neoplasms / metabolism*
  • Nasopharyngeal Neoplasms / radiotherapy
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism*
  • Peptides / pharmacology
  • Radiation Tolerance* / drug effects
  • Signal Transduction
  • Ubiquitination
  • Up-Regulation* / drug effects
  • fas Receptor / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • BIRC7 protein, human
  • FAS protein, human
  • HSF1 protein, human
  • Heat Shock Transcription Factors
  • Inhibitor of Apoptosis Proteins
  • Neoplasm Proteins
  • Peptides
  • fas Receptor

Grants and funding

This study was supported by grants from the National Nature and Science Foundation of China (81870706, 31570932, 81700888, 81701589), Guangdong Provincial Key Laboratory of Regional Immunity and Diseases (2019B030301009) and the Shenzhen Science, Technology and Innovation Committee (JCYJ20170307162827158, KQTD20170331145453160). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.