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EGFR and VEGFR as potential target for biological therapies in HCC cells

Gianluigi Giannelli1, Concetta Sgarra, Letizia Porcelli

  • 1Department of Internal Medicine, Immunology, and Infectious Diseases, Section of Internal Medicine, University of Bari Medical School, Bari, Italy. g.giannelli@intmed.uniba.it

Cancer Letters
|February 6, 2008
PubMed

Insights

Gefitinib and vandetanib inhibit hepatocellular carcinoma (HCC) cell migration and invasion by blocking p-EGFR pathways. These drugs also reduce secretion of MMP-2 and MMP-9, offering potential for HCC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Hepatocellular carcinoma (HCC) is a lethal malignancy with limited therapeutic options.
  • Epidermal Growth Factor Receptor (EGFR) and Vascular Endothelial Growth Factor Receptor (VEGFR) inhibitors are being explored for HCC treatment.

Purpose of the Study:

  • To investigate the effects of gefitinib and vandetanib on HCC cell behavior and signaling pathways.
  • To determine the impact of these inhibitors on matrix metalloproteinase secretion.

Main Methods:

  • Assessing HCC cell migration on Laminin-5 and Fibronectin.
  • Evaluating invasion through matrigel.
  • Analyzing phosphorylation of EGFR, Erk1/2, and Akt.
  • Measuring secretion of matrix metalloproteinases (MMP-2 and MMP-9).

Main Results:

  • Gefitinib and vandetanib inhibited HCC cell migration and invasion.
  • Both drugs reduced p-EGFR levels rapidly, with progressive effects on p-Erk1/2 and p-Akt.
  • PI3K/Akt and MEK/Erk1/2 inhibitors also reduced migration and invasion.
  • Vandetanib and gefitinib decreased MMP-2 and MMP-9 secretion.

Conclusions:

  • Gefitinib and vandetanib exhibit anti-migratory and anti-invasive properties in HCC cells.
  • These effects are mediated through the inhibition of p-EGFR signaling pathways.
  • The drugs down-regulate MMP-2 and MMP-9, suggesting a role in controlling tumor invasion and metastasis.

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