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

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.