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 language | English |
|---|---|
| Pages (from-to) | 479-485 |
| Number of pages | 7 |
| Journal | Biochemical Pharmacology |
| Volume | 71 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Feb 14 2006 |
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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 journal › Article
}
TY - JOUR
T1 - ZD6474 inhibits proliferation and invasion of human hepatocellular carcinoma cells
AU - Giannelli, Gianluigi
AU - Azzariti, Amalia
AU - Sgarra, Concetta
AU - Porcelli, Letizia
AU - Antonaci, Salvatore
AU - Paradiso, Angelo
PY - 2006/2/14
Y1 - 2006/2/14
N2 - 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.
AB - 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.
KW - Biological therapies
KW - Extracellular matrix proteins
KW - Hepatocellular carcinoma
KW - Invasion
KW - Laminin-5
KW - Proliferation
KW - Vascular endothelial growth factor receptor
KW - ZD6474
UR - http://www.scopus.com/inward/record.url?scp=30444451162&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=30444451162&partnerID=8YFLogxK
U2 - 10.1016/j.bcp.2005.11.005
DO - 10.1016/j.bcp.2005.11.005
M3 - Article
C2 - 16332356
AN - SCOPUS:30444451162
VL - 71
SP - 479
EP - 485
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
SN - 0006-2952
IS - 4
ER -