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

Abstract

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, β-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 β-catenin, nuclear factor (NF)κB, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, matrix metalloproteinase (MMP)9, transforming growth factor (TGF)-β1, fibroblast growth factor (FGF)-2 and integrin-β6. 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 α-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 NFκB, TNF-α, IL-1β, TGF-β1, MMP9, FGF-2 and integrin-β6. In conclusion, iCRT14 treatment exhibited antitumor effects against HCC through impairing β-catenin signaling pathway. iCRT14 suppressed liver tissue inflammation, fibrosis and angiogenesis, possibly via reducing expression of NFκB, TNF-α, IL-1β, TGF-β1, MMP-9, FGF-2.

• Authors: Hanan M Hassan, Sherif M H El-Kannishy, Abdullah Alattar, Reem Alshaman, Ahmed M Hamdan, Mohammed M H Al-Gayyar
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 135 Pg. 111216 (Mar 2021) ISSN: 1950-6007 [Electronic] France
• PMID: 33433352 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Antineoplastic Agents
• Ctnnb1 protein, rat
• Cytokines
• Inflammation Mediators
• Pyridines
• Pyrroles
• Tgfb1 protein, rat
• Thiazolidinediones
• Transforming Growth Factor beta1
• beta Catenin
• iCRT14
• Thioacetamide
• Fibroblast Growth Factor 2
• Matrix Metalloproteinase 9
• Mmp9 protein, rat

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Antineoplastic Agents (pharmacology)
• Cell Movement (drug effects)
• Cytokines (genetics, metabolism)
• Fibroblast Growth Factor 2 (genetics, metabolism)
• Fibrosis
• Inflammation Mediators (metabolism)
• Liver Neoplasms, Experimental (chemically induced, drug therapy, metabolism, pathology)
• Male
• Matrix Metalloproteinase 9 (genetics, metabolism)
• Neoplasm Invasiveness
• Neovascularization, Pathologic
• Pyridines (pharmacology)
• Pyrroles (pharmacology)
• Rats, Sprague-Dawley
• Thiazolidinediones (pharmacology)
• Thioacetamide
• Transforming Growth Factor beta1 (genetics, metabolism)
• Wnt Signaling Pathway
• beta Catenin (antagonists & inhibitors, metabolism)