Effect of NLRP3 inhibitor on metastasis in mouse breast cancer model

Objective: This study aimed to investigate the inhibitory effects of MCC950, a specific NLRP3 inhibitor, on bone metastasis and the NLRP3 inflammasome in an orthotopic breast tumor model generated with 4T1.2 cells, using radiological, histopathological, and molecular techniques. Materials and Methods: 4T1.2 tumors were established in female BALB/c mice, and tumor and MCC950 groups were monitored. Mice were scanned with X-ray/DECT, and after sacrifice, tibia/femur samples were decalcified and examined with H&E staining. Tissue samples obtained from primary tumors were stained with NLRP3, caspase-1, and IL-1β primary antibodies via immunohistochemistry, while the pro/active forms of the same antibodies were analyzed by Western blot. Results: No significant difference in primary tumor burden was observed between groups. X-ray/DECT was insufficient due to the small size of mouse bones. Histologically, pathological changes associated with bone metastasis were observed in the tumor group, whereas in the MCC950-treated group, bone structure was preserved and the extent of involvement was more limited. At the molecular level, increased NLRP3 and active caspase-1/IL-1β levels in tumor tissue samples were reduced by MCC950 treatment, while pro-caspase-1 and pro-IL-1β were largely preserved. Conclusion: In the metastatic breast cancer model, MCC950 treatment limited metastatic patterns, and this effect was concluded to be associated with the suppression of the NLRP3 axis through reduced active caspase-1 and mature IL-1β production.