QNZ alleviated hepatocellular carcinoma by targeting inflammatory pathways in a rat model

The pathogenicity of HCC could be enhanced by TNF-alpha and NF kappa B, which are crucial parts of the inflammatory pathway inside the HCC microenvironment. Therefore, we aimed to discover the therapeutic effects of QNZ, an inhibitor of both TNF-alpha and NF kappa B, in an experimental model of HCC in rats. HCC was experimentally induced in rats by thioacetamide, and some of the rats were treated with QNZ. The expression levels of nuclear factor (NF)kappa B, tumor necrosis factor (TNF)-alpha, apoptosis signal regulating kinase (ASK)-1, beta-catenin, glycogen synthase kinase (GSK)-3 and TNF receptor-associated factor (TRAF) were examined in hepatic samples. In addition, hepatic tissues were stained with hematoxylin/eosin and anti-TNF-alpha antibodies. QNZ blocked HCC-induced expression of both NF kappa B and TNF-alpha. It significantly reduced both alpha-fetoprotein and the average number of nodules and increased the survival rate of the HCC rats. Moreover, hematoxylin and eosin liver sections from the HCC rats showed vacuolated cytoplasm and necrotic nodules. All of these effects were alleviated by QNZ treatment. Finally, treating HCC rats with QNZ resulted in a reduction in the expression of TRAF, ASK-1 and beta-catenin, as well as increased expression of GSK-3. In conclusion, inhibition of the inflammatory pathway in HCC with QNZ produced therapeutic effects, as indicated by an increased survival rate, reduced serum alpha-fetoprotein levels, decreased liver nodules and improved the hepatocyte structure. In addition, QNZ significantly reduced the expression of TRAF, ASK-1 and beta-catenin that were associated with increased expression of GSK-3.