Experimental cell research · 2014
Anti-tumor activity of sorafenib in a model of a pediatric hepatocellular carcinoma.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Nagel Carmen, Armeanu-Ebinger Sorin, Dewerth Alexander, Warmann Steven W, Fuchs Jörg
Аннотация
BACKGROUND: Treatment outcome of children with pediatric hepatocellular carcinoma (pHCC) is poor. Therefore, we evaluated the tyrosine kinase inhibitor sorafenib in a model of pHCC.
METHODS: Cell viability after treatment with sorafenib was evaluated in HC-AFW1 cells (pHCC) using MTT assay and compared to an adult HCC (aHCC) and two hepatoblastoma (HB) cell lines. ERK, pERK, E-cadherin, and vimentin expression were investigated using Western Blot. Sorafenib (60 mg/kg) was administered orally to NOD.Cg-Prkdcscid-IL2rgtmWjl/Sz mice bearing subcutaneous HC-AFW1-derived tumors. Tumor progression, viability, and vascularization were monitored by tumor volume, AFP levels, and CD31 immunostaining, respectively. Sensitization to sorafenib was evaluated using the β-catenin inhibitor ICG001.
RESULTS: Sorafenib reduced cell viability in HC-AFW1 (IC50: 8 µM), comparable to HB cells, however less pronounced in aHCC cells (IC50: 23 µM). Sorafenib inhibited ERK signaling in both, HC-AFW1 cells and -xenografts. In vivo, sorafenib treatment only led to a moderate tumor growth inhibition, although significant reduction of vascularization and tumor growth kinetics was observed. Long-term treatment with sorafenib decreased E-cadherin, but showed no induction of vimentin expression. Combining sorafenib with a β-catenin inhibitor led to an additional reduction of cell viability.
CONCLUSION: Sorafenib together with inhibitors of the β-catenin pathway might be an effective tool in the treatment of pediatric HCC.
METHODS: Cell viability after treatment with sorafenib was evaluated in HC-AFW1 cells (pHCC) using MTT assay and compared to an adult HCC (aHCC) and two hepatoblastoma (HB) cell lines. ERK, pERK, E-cadherin, and vimentin expression were investigated using Western Blot. Sorafenib (60 mg/kg) was administered orally to NOD.Cg-Prkdcscid-IL2rgtmWjl/Sz mice bearing subcutaneous HC-AFW1-derived tumors. Tumor progression, viability, and vascularization were monitored by tumor volume, AFP levels, and CD31 immunostaining, respectively. Sensitization to sorafenib was evaluated using the β-catenin inhibitor ICG001.
RESULTS: Sorafenib reduced cell viability in HC-AFW1 (IC50: 8 µM), comparable to HB cells, however less pronounced in aHCC cells (IC50: 23 µM). Sorafenib inhibited ERK signaling in both, HC-AFW1 cells and -xenografts. In vivo, sorafenib treatment only led to a moderate tumor growth inhibition, although significant reduction of vascularization and tumor growth kinetics was observed. Long-term treatment with sorafenib decreased E-cadherin, but showed no induction of vimentin expression. Combining sorafenib with a β-catenin inhibitor led to an additional reduction of cell viability.
CONCLUSION: Sorafenib together with inhibitors of the β-catenin pathway might be an effective tool in the treatment of pediatric HCC.
Предметные рубрики MeSH
AdultAnimalsBlotting, WesternCarcinoma, HepatocellularCell ProliferationChildEpithelial-Mesenchymal TransitionFemaleHumansLiver NeoplasmsMaleMiceMice, Inbred NODMice, SCIDNeovascularization, PathologicNiacinamidePhenylurea CompoundsProtein Kinase InhibitorsSorafenibTumor Cells, CulturedXenograft Model Antitumor Assaysbeta Catenin