Sylvia Muche1, Melissa Kirschnick1, Michael Schwarz1, Albert Braeuning2. 1. Department of Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, University of Tübingen, Tübingen, Germany. 2. Department of Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, University of Tübingen, Tübingen, Germany albert.braeuning@uni-tuebingen.de.
Abstract
BACKGROUND/AIM: The kinase inhibitor sorafenib is the only approved drug which is effective against late-stage hepatocellular carcinoma (HCC). However, the mean survival of patients is still less than one year, making new approaches for tumor treatment essential. Oncogenic signaling through β-catenin is frequently overactivated in HCC and therefore a potential target for a combination therapy with sorafenib. MATERIALS AND METHODS: Two hepatoma cell lines were treated with non-cytotoxic concentrations of sorafenib and different β-catenin inhibitors. The tumor-relevant end-points of proliferation, apoptosis, cell migration, and colony formation were assessed in vitro along with the activity of the Wingless/Int-1(WNT)/β-catenin and mitogen-activated protein kinase pathways. RESULTS: Combined treatment with sorafenib and β-catenin inhibitors synergized in the inhibition of cell proliferation, migration, colony formation ability, and induction of apoptosis. CONCLUSION: In vitro data suggest that the combination of sorafenib and β-catenin inhibition might be a promising approach for HCC treatment. Copyright
BACKGROUND/AIM: The kinase inhibitor sorafenib is the only approved drug which is effective against late-stage hepatocellular carcinoma (HCC). However, the mean survival of patients is still less than one year, making new approaches for tumor treatment essential. Oncogenic signaling through β-catenin is frequently overactivated in HCC and therefore a potential target for a combination therapy with sorafenib. MATERIALS AND METHODS: Two hepatoma cell lines were treated with non-cytotoxic concentrations of sorafenib and different β-catenin inhibitors. The tumor-relevant end-points of proliferation, apoptosis, cell migration, and colony formation were assessed in vitro along with the activity of the Wingless/Int-1(WNT)/β-catenin and mitogen-activated protein kinase pathways. RESULTS: Combined treatment with sorafenib and β-catenin inhibitors synergized in the inhibition of cell proliferation, migration, colony formation ability, and induction of apoptosis. CONCLUSION: In vitro data suggest that the combination of sorafenib and β-catenin inhibition might be a promising approach for HCC treatment. Copyright
Authors: Osman Öcal; Daniel Rössler; Antonio Gasbarrini; Thomas Berg; Heinz-Josef Klümpen; Irene Bargellini; Bora Peynircioglu; Otto van Delden; Christian Schulz; Kerstin Schütte; Roberto Iezzi; Maciej Pech; Peter Malfertheiner; Bruno Sangro; Jens Ricke; Max Seidensticker Journal: J Cancer Res Clin Oncol Date: 2021-09-20 Impact factor: 4.322