Pharmacological inhibition of beta-catenin in hepatoblastoma cells
| Autor: | Joerg Fuchs, Steven W. Warmann, Verena Ellerkamp, Sorin Armeanu-Ebinger, Justus Lieber, Julia Wenz, C. Nagel |
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| Rok vydání: | 2012 |
| Předmět: |
Hepatoblastoma
Cell Survival Antineoplastic Agents Pyrimidinones Proto-Oncogene Mas In vivo Cell Line Tumor medicine Tumor Cells Cultured Humans Tissue Distribution Viability assay Etodolac Protein Kinase Inhibitors beta Catenin Cell Proliferation Cisplatin Sulfonamides Cell growth business.industry Liver Neoplasms Wnt signaling pathway General Medicine medicine.disease Bridged Bicyclo Compounds Heterocyclic Cell culture Celecoxib Pediatrics Perinatology and Child Health Cancer research Pyrazoles Surgery business medicine.drug |
| Zdroj: | Pediatric surgery international. 29(2) |
| ISSN: | 1437-9813 |
| Popis: | The proto-oncogene beta-catenin is linked to an abnormal activation of the Wnt/beta-catenin-pathway and shows mutations in 50–90 % of hepatoblastoma (HB). Corresponding, the recently published murine orthotopic HB model differs from the former subcutaneous model by nuclear beta-catenin distribution. As the nuclear localization of beta-catenin is considered to reflect a more aggressive tumor growth, the influence of beta-catenin inhibition on cell viability and drug-efficiency in HB cells was analyzed. Beta-catenin distribution in HB cells was analyzed by immunofluorescence. The influence of beta-catenin inhibitors Celecoxib, Etodolac, ICG001, and MET kinase inhibitor (SU11274) alone and in combination with cisplatin (CDDP) on HB cell lines (HuH6, HepT1) was evaluated by cell viability assays and BrdU incorporation. Celecoxib and ICG001 reduced dose-dependently HB cell viability and decreased nuclear beta-catenin in cultivated HB cells. Etodolac was without influence at concentrations up to 100 μM. Combinations of Celecoxib or ICG001 with MET kinase inhibitor or CDDP resulted in additive reduction of cell viability. Pharmaceutical beta-catenin inhibitors can modulate the nuclear localization of beta-catenin and reduce cell viability of HB cells in vitro. These promising effects might optimize the outcome of high-risk HB. The orthotopic HB model is a suitable basis for further in vivo studies. |
| Databáze: | OpenAIRE |
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