Effects of Wnt‑1 blockade in DEN‑induced hepatocellular adenomas of mice

Sklavos,Argyrios; Poutahidis,Theofilos; Giakoustidis,Alexander; Makedou,Kali; Angelopoulou,Katerina; Hardas,Alexander; Andreani,Paola; Zacharioudaki,Argyro; Saridis,George; Goulopoulos,Thomas; Tsarea,Kalliopi; Karamperi,Maria; Papadopoulos,Vassilios; Papanikolaou,Vassilios; Papalois,Apostolos; Iliadis,Stavros; Mudan,Satvinder; Azoulay,Daniel; Giakoustidis,Dimitrios

doi:10.3892/ol.2017.7427

Effects of Wnt‑1 blockade in DEN‑induced hepatocellular adenomas of mice

Authors:
- Argyrios Sklavos
- Theofilos Poutahidis
- Alexander Giakoustidis
- Kali Makedou
- Katerina Angelopoulou
- Alexander Hardas
- Paola Andreani
- Argyro Zacharioudaki
- George Saridis
- Thomas Goulopoulos
- Kalliopi Tsarea
- Maria Karamperi
- Vassilios Papadopoulos
- Vassilios Papanikolaou
- Apostolos Papalois
- Stavros Iliadis
- Satvinder Mudan
- Daniel Azoulay
- Dimitrios Giakoustidis
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Affiliations: Division of Transplant Surgery, Department of Surgery, School of Medicine, Faculty of Health Sciences, Aristotle University and Hippokration General Hospital, Thessaloniki 54642, Greece, Laboratory of Pathology, School of Veterinary Medicine, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece, Academic Department of Surgery, The Royal Marsden Hospital, London SW3 6JJ, UK, Laboratory of Biochemistry, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece, Laboratory of Biochemistry and Toxicology, School of Veterinary Medicine, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece, Service de Chirurgie Digestive et Hépatobiliaire, Hôpital Henri Mondor, Assistance Publique‑Hôpitaux de Paris‑Université Paris‑Est, Créteil 94000, France, Experimental and Research Center ELPEN Pharmaceuticals, Athens 19009, Greece, Propedeutic Division of Surgery, Department of Surgery School of Medicine, Faculty of Health Sciences, Aristotle University and AHEPA University Hospital, Thessaloniki 54124, Greece
Published online on: November 15, 2017 https://doi.org/10.3892/ol.2017.7427
Pages: 1211-1219

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Abstract

Recent evidence has suggested that downregulation of the Wnt/β‑catenin signaling pathway may contribute to the development and growth of HCC. Consequently, elements of this pathway have begun to emerge as potential targets for improving outcomes of anti‑HCC. Thus, the present study sought to examine the effects of Wnt‑1 blockade using the classical diethylnitrosamine (DEN)‑induced chemical carcinogenesis mouse model of HCC. The depletion of Wnt‑1 using neutralizing antisera was done for ten consecutive days at the age of 9 months and mice were examined for the following 20 days. At that time, DEN‑treated mice had multiple variably‑sized hepatic cell adenomas. Anti‑Wnt‑1 was particularly potent in suppressing the expression of critical elements of the Wnt/β‑catenin signaling pathway, such as β‑catenin and Frizzled‑1 receptor, however, not Dickkopf‑related protein 1. This effect co‑existed with the suppression of Cyclin D1, FOXM1, NF‑κΒ and c‑Jun commensurate with proliferation and apoptosis blockade in hepatocellular adenomas, and reduced Bcl‑2 and c‑Met in the serum of mice. Nonetheless, tumor size and multiplicity were found to be unaffected, suggesting that apoptosis may be equally important to proliferation in the context of counteracting DEN induced hepatocellular adenomas of mice.

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