Therapeutic effects of blocking β-catenin against hepatocellular carcinoma-induced activation of inflammation, fibrosis and tumor invasion

Destructive effects of hepatocellular carcinoma (HCC) is enhanced by many cellular mechanisms including activation of fibrosis, inflammation and tumor invasion. Therefore, this study was conducted to investigate the therapeutic effects of iCRT14, beta-catenin blocker, on HCC. In addition, the molecular effects of iCRT14 will be investigated on inflammation, fibrosis and tumor invasion pathways. After inducting HCC in rats, hepatic tissues were used for determination of the expression of beta-catenin, nuclear factor (NF)kappa B, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, matrix metalloproteinase (MMP)9, transforming growth factor (TGF)-beta 1, fibroblast growth factor (FGF)-2 and integrin-beta 6. Hepatic tissues were stained with hematoxylin/eosin and with anti-Ki67. Results revealed that iCRT14 significantly increased the survival percent of HCC rats, reduced both alpha-fetoprotein and average number of nodules. In parallel, hepatic sections from HCC rats stained with hematoxylin/eosin revealed vacuolated cytoplasm and necrotic nodules, which were attenuated by treatment with iCRT14. Finally, treating HCC rats with iCRT14 resulted in reduction of the expression of NF kappa B, TNF-alpha, TGF-beta 1, MMP9, FGF-2 and integrin-beta 6. In conclusion, iCRT14 treatment exhibited antitumor effects against HCC through impairing beta-catenin signaling pathway. iCRT14 suppressed liver tissue inflammation, fibrosis and angiogenesis, possibly via reducing expression of NF kappa B, TNF-alpha, IL-1 beta, TGF-beta 1, MMP-9, FGF-2.

Automated summary

iCRT14 treatment showed significant antitumor effects against hepatocellular carcinoma (HCC) in rats by increasing survival rate, reducing alpha-fetoprotein levels, and decreasing the average number of nodules. It also attenuated hepatic tissue damage and inflammation by suppressing the expression of specific proteins.