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 journalArticle

38 Citations (Scopus)

Abstract

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
Volume71
Issue number4
DOIs
Publication statusPublished - Feb 14 2006

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Hepatocellular Carcinoma
Cells
Extracellular Matrix Proteins
Vascular Endothelial Growth Factor Receptor
Cell adhesion
Blood vessels
Cell proliferation
Cell growth
Growth
Cell Adhesion
Pharmaceutical Preparations
Cell Movement
Blood Vessels
N-(4-bromo-2-fluorophenyl)-6-methoxy-7-((1-methylpiperidin-4-yl)methoxy)quinazolin-4-amine
Tumors
Adhesion
Cell Proliferation
Modulation
Apoptosis
Cell Line

Keywords

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

ASJC Scopus subject areas

  • Pharmacology

Cite this

ZD6474 inhibits proliferation and invasion of human hepatocellular carcinoma cells. / Giannelli, Gianluigi; Azzariti, Amalia; Sgarra, Concetta; Porcelli, Letizia; Antonaci, Salvatore; Paradiso, Angelo.

In: Biochemical Pharmacology, Vol. 71, No. 4, 14.02.2006, p. 479-485.

Research output: Contribution to journalArticle

Giannelli, Gianluigi ; Azzariti, Amalia ; Sgarra, Concetta ; Porcelli, Letizia ; Antonaci, Salvatore ; Paradiso, Angelo. / ZD6474 inhibits proliferation and invasion of human hepatocellular carcinoma cells. In: Biochemical Pharmacology. 2006 ; Vol. 71, No. 4. pp. 479-485.
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