Universität zu Köln

Nass, Norbert ORCID: 0000-0003-2563-0386, Streit, Sebastian, Wybranski, Christian, Juergens, Julian, Brauner, Jan, Schulz, Nadine, Powerski, Maciej, Ricke, Jens, Kalinski, Thomas, Dudeck, Oliver and Seidensticker, Max ORCID: 0000-0002-2481-5410 (2017). Validation of VX2 as a Hepatocellular Carcinoma Model: Comparison of the Molecular Reaction of VX2 and HepG2 Tumor Cells to Sorafenib In Vitro. Anticancer Res., 37 (1). S. 87 - 94. ATHENS: INT INST ANTICANCER RESEARCH. ISSN 1791-7530

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Abstract

As there is currently no superior hepatocellular carcinoma (HCC) model with percutaneous vascular access for transarterial treatments available, the VX2 rabbit model is frequently used for in vivo investigations on liver carcinoma. However, the VX2 cell line was derived from a virus-induced skin papilloma that can form carcinosarcoma in liver of rabbits and the transferability of obtained results to HCC treatment remains open. Here we compared the most frequently investigated human HCC model cell line, HepG2, with VX2 cells in vitro in terms of sensitivity towards the broad specificity kinase inhibitor sorafenib and responsiveness to the addition of platelet-derived growth factor AB (PDGF-AB), vascular endothelial growth factor (VEGF) and hepatic growth factor (HGF), as well as insulin and interleukin-1 beta (IL1 beta). Phosphorylation of protein kinase B (AKT) the mitogen-activated protein kinases (MAPKs) p38 and p42/44 (extracellular signal-regulated kinase, ERK1/2) and inhibitor of kappa light chain gene enhancer alpha (I kappa B alpha) was determined by western blotting as these events are associated with early signaling cascades. Additionally, the inhibition of phosphorylation under sorafenib treatment was investigated. Sorafenib was equally toxic to both cell lines, but only in HepG2 was activation of caspase 3/7 activity, as a sign of apoptosis, observed. VX2 cells exhibited generally more intense phosphorylation signals in response to the growth factors and also serum. In contrast to VX2, HepG2 cells showed no response to PDGF-AB or VEGF as determined by kinase phosphorylation. In both cell lines, sorafenib inhibited growth factor-induced phosphorylation of ERK and p38-MAPK. AKT phosphorylation was only inhibited in VX2 cells and I kappa B alpha phosphorylation was not influenced by this kinase inhibitor in either cell type. Taken together, the two cellular models for HCC share several features related to sorafenib application, but differed in their responsiveness towards growth factors. Therefore, results obtained with the VX2 model cannot be extended to human HCC without appropriate caution.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Nass, Norbert UNSPECIFIED orcid.org/0000-0003-2563-0386 UNSPECIFIED Streit, Sebastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Wybranski, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Juergens, Julian UNSPECIFIED UNSPECIFIED UNSPECIFIED Brauner, Jan UNSPECIFIED UNSPECIFIED UNSPECIFIED Schulz, Nadine UNSPECIFIED UNSPECIFIED UNSPECIFIED Powerski, Maciej UNSPECIFIED UNSPECIFIED UNSPECIFIED Ricke, Jens UNSPECIFIED UNSPECIFIED UNSPECIFIED Kalinski, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Dudeck, Oliver UNSPECIFIED UNSPECIFIED UNSPECIFIED Seidensticker, Max UNSPECIFIED orcid.org/0000-0002-2481-5410 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-242928
DOI:	10.21873/anticanres.11293
Journal or Publication Title:	Anticancer Res.
Volume:	37
Number:	1
Page Range:	S. 87 - 94
Date:	2017
Publisher:	INT INST ANTICANCER RESEARCH
Place of Publication:	ATHENS
ISSN:	1791-7530
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language LIVER-TUMOR; RAF/MEK/ERK PATHWAY; GROWTH-FACTOR; KINASE 1; CHEMOEMBOLIZATION; PROLIFERATION; EMBOLIZATION; FEASIBILITY; EXPRESSION; THERAPY Multiple languages Oncology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/24292