The dual EGF/VEGF receptor tyrosine kinase inhibitor AEE788 inhibits growth of human hepatocellular carcinoma xenografts in nude mice

  • Authors: Kinya Okamoto, Daniel Neureiter, Beate Alinger, Matthias Meissnitzer, Gabriele Sass, Volker Schmitz, Pietro Di Fazio, Till Wissniowski, Susanne Gahr, Bernd Hohenstein, Bernhard Kaufmann, Axel Schlösser, Ulrike Haus, Eckhart G. Hahn, Christoph Herold, Matthias Ocker
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  • Published online on: Wednesday, October 1, 2008
  • Pages: 733-742
  • DOI: 10.3892/ijo_00000059

Abstract

We investigated the effect of AEE788, a novel dual receptor tyrosine kinase inhibitor of the EGF and the VEGF receptor, for treatment of human HCC cell lines and in a subcutaneous xenograft model. Cell viability and apoptosis of HepG2 and Hep3B cells incubated with 0.1-100 µM AEE788 were quantified. In vivo, HepG2 cells were xenografted to NMRI mice and animals were treated orally with 50 mg/kg AEE788 3x/week. Immunohistochemistry and quantitative Western blotting was performed for pathway analysis in vitro and in vivo. AEE788 reduced growth and induced apoptosis of HCC cells by disrupting mitochondrial transmembrane potentials and inhibiting MAPK phosphorylation. In the xenografts, AEE788 lead to a reduced tumor growth by reducing proliferation and vascularisation. Except for a reversible skin reaction and weight loss, no signs of toxicity were observed. AEE788 is a promising new option for the treatment of HCC.
Journal Cover

October 2008
Volume 33 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

2013 Impact Factor: 2.773
Ranked #30/202 Oncology
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APA
Okamoto, K., Neureiter, D., Alinger, B., Meissnitzer, M., Sass, G., Schmitz, V., Di Fazio, P., Wissniowski, T., Gahr, S., Hohenstein, B., Kaufmann, B., Schlösser, A., Haus, U., Hahn, E., Herold, C., & Ocker, M. (2008). The dual EGF/VEGF receptor tyrosine kinase inhibitor AEE788 inhibits growth of human hepatocellular carcinoma xenografts in nude mice. International Journal of Oncology, 33(4), 733-742.
MLA
Okamoto, Neureiter, Alinger, Meissnitzer, Sass, Schmitz, Di Fazio, Wissniowski, Gahr, Hohenstein, Kaufmann, Schlösser, Haus, Hahn, Herold, and Matthias Ocker. "The dual EGF/VEGF receptor tyrosine kinase inhibitor AEE788 inhibits growth of human hepatocellular carcinoma xenografts in nude mice." International Journal of Oncology International Journal of Oncology 33.4 (2008): 733-742.
Chicago
Okamoto, Neureiter, Alinger, Meissnitzer, Sass, Schmitz, Di Fazio, Wissniowski, Gahr, Hohenstein, Kaufmann, Schlösser, Haus, Hahn, Herold, and Matthias Ocker. "The dual EGF/VEGF receptor tyrosine kinase inhibitor AEE788 inhibits growth of human hepatocellular carcinoma xenografts in nude mice." International Journal of Oncology International Journal of Oncology 33 no. 4 (2008): 733-742.