Peroxiredoxin 1 inhibits tumorigenesis by activating the NLRP3/GSDMD pathway to induce pyroptosis of colorectal cancer cells

doi:10.3748/wjg.v31.i36.111557

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Sep 28, 2025 (publication date) through Sep 19, 2025

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Basic Study

World J Gastroenterol. Sep 28, 2025; 31(36): 111557
Published online Sep 28, 2025. doi: 10.3748/wjg.v31.i36.111557

Peroxiredoxin 1 inhibits tumorigenesis by activating the NLRP3/GSDMD pathway to induce pyroptosis of colorectal cancer cells

Ying He, Jing Liu, Ning Zhou, Ling-Xiang Xie, Yong-Fang Jiang, Chun-Lan Chen

Ying He, Jing Liu, Ning Zhou, Yong-Fang Jiang, Department of Infectious Diseases, The Second Xiangya Hospital of Central South University, Clinical Medical Research Center for Viral Hepatitis in Hunan Province, Changsha 410011, Hunan Province, China

Ling-Xiang Xie, National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China

Chun-Lan Chen, Department of Pulmonary and Critical Care Medicine, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha 410005, Hunan Province, China

Co-corresponding authors: Chun-Lan Chen and Yong-Fang Jiang.

Author contributions: Chen CL and Jiang YF generated the hypothesis and designed the experiments. He Y, Liu J, Zhou N, and Xie LX performed the experiments; He Y and Chen CL interpreted the data. Chen CL, He Y, and Jiang YF wrote the manuscript. All authors have read and approved the final version to be published. Both Chen CL and Jiang YF have played important and indispensable roles in the experimental design, data interpretation and manuscript preparation as the co-corresponding authors.

Supported by the National Natural Science Foundation of China, No. 82302454; Natural Science Foundation of Hunan Province, No. 2025JJ60797, No. 2025JJ60734 and No. 2022JJ40718; and Guangdong Basic and Applied Basic Research Foundation, No. 2022A1515111063.

Institutional review board statement: The study was approved by the Ethics Committee of The Second Xiangya Hospital of Central South University for the studies involving humans (Ethics No. LYEC2025-K0057). The study was conducted in accordance with the local legislation and institutional requirements.

Institutional animal care and use committee statement: Animal care was provided in compliance with the Guidelines for the Care and Use of Laboratory Animals published by the National Institutes of Health. The experimental protocol was approved by the Ethics Review Committee for Animal Experimentation of Central South University, No. 20240728.

Conflict-of-interest statement: The authors declare that they have no conflicts of interest.

ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.

Data sharing statement: Data are available upon reasonable requests from the corresponding author.

Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/

Corresponding author: Chun-Lan Chen, PhD, Department of Pulmonary and Critical Care Medicine, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, No. 61 Jiefang Road, Furong District, Changsha 410005, Hunan Province, China. cclen208@163.com

Received: July 3, 2025
Revised: August 6, 2025
Accepted: August 25, 2025
Published online: September 28, 2025
Processing time: 78 Days and 16.5 Hours

Abstract

BACKGROUND

Damage associated molecular patterns (DAMPs) are vital for the immunogenic cell death of cancer cells and can enhance the anti-tumor activity of immune cells in colorectal cancer (CRC). Peroxiredoxin 1 (Prdx1), an important DAMP, is highly expressed in various tumor tissues including CRC. However, the role of Prdx1 in CRC remains unknown.

AIM

To investigate the effect and mechanisms of Prdx1 on CRC.

METHODS

Patients diagnosed with CRC in our medical center were included in this study to verify the expression of Prdx1 in cancer tissues. Recombinant Prdx1 (rPrdx1) was used to stimulate RKO and SW480 colon cancer cells. The cell survival rate, migration, proliferation and invasion ability were assessed. Transmission electron microscopy, TUNEL assay, lactate dehydrogenase release assay, and Western blot were used to determine the effect of Prdx1 on pyroptosis. NLRP3 inflammasome inhibitor and gasdermin D (GSDMD) inhibitor were used to explore the mechanism of Prdx1-induced pyroptosis.

RESULTS

The mRNA and protein levels of Prdx1 were significantly increased in the tumor tissues of patients with CRC. rPrdx1 inhibited the viability, proliferation, migration and invasion of RKO and SW480 colon cancer cells. Further study found that rPrdx1 inhibited the malignant biological behaviors of CRC cells by inducing pyroptosis rather than apoptosis and necroptosis. Mechanistically, rPrdx1 induces pyroptosis of CRC cells by activating the NLRP3 inflammasome/GSDMD pathway.

CONCLUSION

Prdx1 induces pyroptosis by activating the NLRP3 inflammasome/GSDMD pathway, thereby inhibiting the malignant biological behavior of RKO and SW480 colon cancer cells.

Keywords: Colorectal cancer; Peroxiredoxin 1; Damage associated molecular patterns; Pyroptosis; Gasdermin D

Core Tip: Peroxiredoxin 1 (Prdx1) as a damage associated molecular pattern could inhibit the viability, proliferation, migration and invasion of RKO and SW480 cells; mechanistically, Prdx1 activates NLRP3 inflammasome/gasdermin D (GSDMD) pathway to induce pyroptosis of colorectal cancer cells. In conclusion, our findings demonstrated that Prdx1 induces pyroptosis by activating NLRP3 inflammasome/GSDMD pathway, thereby inhibiting the malignant biological behavior of RKO and SW480 colon cancer cells.