Monitoring and Regulating Intracellular GPX4 mRNA Using Gold Nanoflare Probes and Enhancing Erastin-Induced Ferroptosis

Biosensors (Basel). 2022 Dec 17;12(12):1178. doi: 10.3390/bios12121178.

Abstract

Glutathione peroxidase 4 (GPX4) plays an important effect on ferroptosis. Down-regulating the expression of GPX4 mRNA can decrease the content of GPX4. In this work, a gold nanoflare (AuNF) probe loaded with anti-sense sequences targeting for GPX4 mRNA was designed to monitor and down-regulate intracellular GPX4 mRNA using fluorescence imaging in situ and using anti-sense technology. The results revealed that there was a marked difference for the expression of GPX4 mRNA in different cell lines, and the survival rate of cancer cells was not significantly effected when the relative mRNA and protein expression levels of GPX4 was down-regulated by AuNF probes. However, when co-treated with AuNF probes, the low expression of GPX4 strengthened erastin-induced ferroptosis, and this synergy showed a better effect on inhibiting the proliferation of cancer cells.

Keywords: AuNF probe; GPX4 mRNA; ferroptosis.

MeSH terms

  • Cell Line
  • Ferroptosis* / genetics
  • Glutathione Peroxidase / genetics
  • Glutathione Peroxidase / metabolism
  • Glutathione Peroxidase / pharmacology
  • Piperazines / pharmacology

Substances

  • Glutathione Peroxidase
  • erastin
  • Piperazines

Grants and funding

The work was supported by the Natural Science Foundation of Shandong Province (Grant No. ZR2015BM024), The Ministry of Education industry-school cooperative education project (Grant No. 220605042200513), the Tai-Shan Scholar Research Fund of Shandong Province, and Research Foundation of Liaocheng University (Grant No. 318012026).