ZD6474 inhibits proliferation and invasion of human hepatocellular carcinoma cells

Gianluigi Giannelli, Amalia Azzariti, Concetta Sgarra, Letizia Porcelli, Salvatore Antonaci, Angelo Paradiso

Research output: Contribution to journalArticlepeer-review


Hepatocellular carcinoma (HCC) is characterized by hypervascularization, neoangiogenesis formation and blood vessel invasion. Recently, it has been demonstrated that an inhibitor of the vascular endothelial growth factor (VEGF) receptor, ZD6474, may directly inhibit the growth of tumor cells. ZD6474 effectiveness was investigated on cell growth, apoptosis, adhesion, migration and invasion and related to the drug-dependent modulation of main molecular targets on HCC cells. ZD6474 inhibited HCC cell proliferation, however, such effect was reverted by Laminin-5 (Ln-5) but not by other extracellular matrix proteins (ECM). ZD6474 also inhibited HCC cell adhesion, migration and invasion, whereas the simultaneous treatment with the drug and Ln-5 strongly recovered those effects. Under the same experimental conditions, ZD6474 inhibited the expression of phosphorylated EGFR in all cell lines while the effect on p-Erk1/2 was dependent on cellular invasive characteristics. Nonetheless, co-incubation with Ln-5 completely recovered this effect. Our results support the hypothesis that ZD6474 could represent an interesting therapeutic opportunity for patients with HCC scarcely expressing the ECM protein, Ln-5.

Original languageEnglish
Pages (from-to)479-485
Number of pages7
JournalBiochemical Pharmacology
Issue number4
Publication statusPublished - Feb 14 2006


  • Biological therapies
  • Extracellular matrix proteins
  • Hepatocellular carcinoma
  • Invasion
  • Laminin-5
  • Proliferation
  • Vascular endothelial growth factor receptor
  • ZD6474

ASJC Scopus subject areas

  • Pharmacology


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