The synergistic effects of PRDX5 and Nrf2 on lung cancer progression and drug resistance under oxidative stress in the zebrafish models

Oncol Res. 2023 Jan 5;30(2):53-64. doi: 10.32604/or.2022.026302. eCollection 2022.

Abstract

Previous studies have shown that PRDX5 and Nrf2 are antioxidant proteins related to abnormal reactive oxidative species (ROS). PRDX5 and Nrf2 play a critical role in the progression of inflammations and tumors. The combination of PRDX5 and Nrf2 was examined by Co-immunoprecipitation, western blotting and Immunohistochemistry. H2O2 was applied to affect the production of ROS and induced multi-resistant protein 1 (MRP1) expression in NSCLC cells. The zebrafish models mainly investigated the synergistic effects of PRDX5 and Nrf2 on lung cancer drug resistance under oxidative stress. We showed that PRDX5 and Nrf2 form a complex and significantly increase the NSCLC tissues compared to adjacent tissues. The oxidative stress improved the combination of PRDX5 and Nrf2. We demonstrated that the synergy between PRDX5 and Nrf2 is positively related to the proliferation and drug resistance of NSCLC cells in the zebrafish models. In conclusion, our data indicated that PRDX5 could bind to Nrf2 and has a synergistic effect with Nrf2. Meanwhile, in the zebrafish models, PRDX5 and Nrf2 have significant regulatory impacts on lung cancer progression and drug resistance activities under oxidative stress.

Keywords: Drug resistance; Lung cancer; Nrf2; Oxidative stress; PRDX5; Zebrafish models.

MeSH terms

  • Animals
  • Carcinoma, Non-Small-Cell Lung*
  • Drug Resistance, Neoplasm
  • Humans
  • Hydrogen Peroxide
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • NF-E2-Related Factor 2 / genetics
  • Oxidative Stress
  • Peroxiredoxins / genetics
  • Reactive Oxygen Species
  • Zebrafish

Substances

  • Hydrogen Peroxide
  • NF-E2-Related Factor 2
  • nfe2l2a protein, zebrafish
  • Peroxiredoxins
  • PRDX5 protein, human
  • Reactive Oxygen Species
  • prdx5 protein, zebrafish