Open Access

ARTICLE

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

SITONG QIAN^1,2,#, YING FANG^1,#, CHENGYUN YAO^1,#, YONGSHENG WANG^3,#, ZHI ZHANG¹, XIAOHUA WANG¹, JIN GAO¹, YONG FENG¹, LEI SUN¹, RUNYUE ZOU², GUOREN ZHOU^1,*, JINJUN YE^1,*, RUIXUE XIA^4,*, HONGPING XIA^5,6,*

1 Jiangsu Cancer Hospital, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Institute of Cancer Research, Nanjing, 210009, China
2 School of Life Sciences, Nanjing Normal University, Nanjing, 210046, China
3 Department of Respiratory Medicine, Nanjing Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing, 210008, China
4 Medical College of Henan University & Henan University Huaihe Hospital, Kaifeng, 475000, China
5Zhongda Hospital, School of Medicine & Advanced Institute for Life and Health, Southeast University, Nanjing, 210009, China
6 Department of Pathology, Nanjing Drum Tower Hospital & Drum Tower Clinical College & School of Basic Medical Sciences & Key Laboratory of Antibody Technique of National Health Commission & Jiangsu Antibody Drug Engineering Research Center, Nanjing Medical University, Nanjing, 211166, China

* Corresponding Authors: GUOREN ZHOU. Email: ; JINJUN YE. Email: ; RUIXUE XIA. Email: ; HONGPING XIA. Email:

Oncology Research 2022, 30(2), 53-64. https://doi.org/10.32604/or.2022.026302

Received 29 August 2022; Accepted 15 November 2022; Issue published 05 January 2023

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.

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Keywords

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