Treatment effects of the multikinase inhibitor sorafenib on hepatoblastoma cell lines and xenografts in NMRI‐Foxn1^nu mice

Abstract

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.

Anti-tumor activity of sorafenib in a model of a pediatric hepatocellular carcinoma

“…Tumor cell proliferation in the HC-AFW1 cell line was effectively inhibited by sorafenib, as it has been previously demonstrated for hepatoblastoma [15]. Growth inhibition of 50% was assessed at nearly the same concentrations found in the HB cell lines HUH6 and HepT1.…”

“…To evaluate tumor response, tissue histology and mean vascular density (MDV) were performed as previously described [15,16]. Capillaries were revealed by CD31-immunostaining using the monoclonal rat anti-mouse CD31 antibody (1:20; Dianova, Hamburg, Germany) and the Avidin-biotin-peroxidase-complex (Linaris, Wertheim, Germany) according to manufacturer's protocol.…”

“…Cells were stimulated with 10% FCS for 10 min before lysis or were left untreated. ERK and phosphorylated ERK (pERK) were assessed using electrophoresis and western blot as previously described [15,16].…”

“…Inhibiting angiogenesis and signal transduction through the Raf/Mek/ERK pathway, sorafenib was approved for treatment of liver and renal carcinoma in adults [13,14]. Moreover, sorafenib also showed a high anti-tumoral activity in pediatric liver tumors like Hepatoblastoma in preclinical studies [15,16]. A pilot study considered sorafenib in combination with cisplatin and doxorubicin in pHCC [7].…”

In vitro evaluation of the Aurora kinase inhibitor VX-680 for Hepatoblastoma

“…Tumor tissue from xenografts of HUH6 and HepT1 were from a previously described experiment [23,25]. Primary HB samples were collected for expression analysis after obtaining informed consent from the patient's parents.…”