Inhibition of NLRP3 inflammasome activation alleviated liver injury and wasting effect in tumor-bearing mice.

This study is designed to evaluate the changes in tumor-bearing mice, as well as to assess the role of NLRP3 in muscle atrophy and its function in the liver of tumor-bearing mice. In this study, RNA-seq data from the liver of Colon26 (C26) tumor-bearing mice were used to perform pathway enrichment analysis. We established a cancer cachexia model by subcutaneous injection of C26 cells, MCC950 was injected intraperitoneally at a concentration of 30 mg/kg on day 12. On day 21, the mice were dissected, the tissues were weighed, and the specimens were fixed for subsequent staining. In our study, by analyzing RNA-seq data, we found that the inflammatory response was significantly activated in the liver of Colon26 (C26) tumor-bearing mice with up-regulation of several inflammatory cytokines, including IL-1β. Therefore, we examined the expression of NLRP3 inflammasome-related genes and found that the expression of most genes was upregulated, and the expression of NLRP3, caspase-1 and IL-1β were also upregulated. This proves that NLRP3 inflammasome is activated in the liver. In our study, on the one hand, we found that inhibition of NLRP3 inflammasome activation could alleviate liver injury and fibrosis in tumor-bearing mice. on the other hand, inhibition of NLRP3 inflammasome activation alleviates muscle atrophy and fat loss. In addition, MCC950 did not affect tumor growth and had no significant effect on the induced consumption of tumor-secreted factors. This study is the first to show that the NLRP3 inflammasome is activated in the liver of tumor-bearing mice. Pharmacological inhibition of NLRP3 inflammasome activation effectively reduces liver injury and fibrosis. Moreover, muscle atrophy and fat loss had also been alleviated.