Treatment effects of the multikinase inhibitor sorafenib on hepatoblastoma cell lines and xenografts in NMRI-Foxn1nu mice
Article first published online: 18 DEC 2011
© 2011 John Wiley & Sons A/S
Volume 32, Issue 4, pages 574–581, April 2012
How to Cite
Eicher, C., Dewerth, A., Kirchner, B., Warmann, S. W., Fuchs, J. and Armeanu-Ebinger, S. (2012), Treatment effects of the multikinase inhibitor sorafenib on hepatoblastoma cell lines and xenografts in NMRI-Foxn1nu mice. Liver International, 32: 574–581. doi: 10.1111/j.1478-3231.2011.02729.x
- Issue published online: 8 MAR 2012
- Article first published online: 18 DEC 2011
- Manuscript Accepted: 22 NOV 2011
- Manuscript Received: 29 APR 2011
- Faculty of Medicine, University of Tuebingen. Grant Number: 1830-0-0
- kinase inhibitor;
- tumour growth;
Multidrug resistance is a major reason for poor treatment results in advanced hepatoblastoma (HB). Several alternative treatment options are currently under investigation to improve the prognosis of affected patients
This study aimed to analyse the impact of sorafenib on the viability of HB cells and xenotransplanted HB tumours.
Cell viability and apoptosis were evaluated in two HB cell lines (HUH6 and HepT1) after treatment with sorafenib using MTT and Caspase 3 activation assay. Extracellular signal-regulated kinase (ERK) phosphorylation was investigated using Western blot. In addition, sorafenib (30 mg/kg) was administered orally to NMRI mice bearing subcutaneous HUH6 derived tumours. Tumour progression and viability were monitored by tumour volume and α-fetoprotein (AFP) levels, and apoptosis was assessed using TUNEL assay. Tumour angiogenesis and mean vascular density (MVD) was determined using CD31 staining, ERK phosphorylation was detected using indirect immunofluorescence.
Treatment with sorafenib led to decreased ERK phosphorylation, reduced cell viability and induction of apoptosis in HepT1 and HUH6 cells. In HB xenografts, sorafenib significantly reduced tumour growth compared with control (P < 0.05). AFP levels were lower in the sorafenib group (P = 0.07). Relative apoptotic areas detected using TUNEL assay were increased (P = 0.003). CD31 staining revealed inhibition of angiogenesis, and mean vascular density was lower in the sorafenib group (P = 0.02). ERK phosphorylation was reduced in tumours tissues after sorafenib treatment.
Treatment with sorafenib led to a potent inhibition of cell viability, tumour progression and angiogenesis. Sorafenib might therefore also be a promising treatment option for high risk or recurrent HB.