Cytochrome P450 2E1 inhibitor Q11 is effective on hepatocellular carcinoma by promoting peritumor neutrophil chemotaxis

Current studies found that the peritumoral tissue of hepatocellular carcinoma (HCC) may be different from normal liver tissue based on proteomics, and related to progression, recurrence and metastasis of HCC. Our previous study proposed "peritumor microenvironment (PME)" to summarize the influence of peritumor tissue on occurrence and progression of HCC. Peritumor CYP2E1 activity was significantly elevated in HCC, and related to occurrence and progression of HCC. However, the effectiveness and mechanism of inhibiting CYP2E1 against HCC remain unclear. In this study, by integrating the advantages of proteomics and transcriptomics, we reanalyzed the various influencing factors in PME. Although there were large differences in the occurrence and progression, the immunity and inflammation still played crucial roles. Peritumor neutrophil were "pro-tumor" phenotype in the stage of progression, while it showed cytotoxicity for tumor cell in the occurrence stage. CYP2E1 activity is associated with peritumor neutrophil infiltration and occurrence of HCC. CYP2E1 inhibitor Q11 showed anti-tumor effects in an orthotopic HCC mouse model by promoting secretion of chemokines and infiltration of neutrophils in peritumor tissue. Overall, these findings provided a reasonable mechanism of anti-tumor effects of CYP2E1 inhibitors, which may be a new strategy for the prevention and treatment of HCC.