ZD6474 inhibits proliferation and invasion of human hepatocellular carcinoma cells

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

doi:10.1016/j.bcp.2005.11.005

Cited by 35 publications

(26 citation statements)

References 32 publications

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“…In their in vitro study, Giannelli and colleagues (25) reported that vandetanib blocked the proliferation, adhesion, migration, and invasion of hepatoma cells via inhibition of the EGFR pathway. Several studies have investigated tumor cell proliferation and metastasis (16,25,26), as well as the correlation between angiogenesis and tumor metastasis (27). What are the mechanisms of vandetanib-induced suppression of intrahepatic macrometastasis?…”

Section: Discussionmentioning

confidence: 99%

Vandetanib, an Inhibitor of VEGF Receptor-2 and EGF Receptor, Suppresses Tumor Development and Improves Prognosis of Liver Cancer in Mice

Inoue

Torimura

Nakamura

et al. 2012

Clinical Cancer Research

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Purpose: VEGF, EGF, and TGF-a are expressed in hepatocellular carcinomas (HCC) and play a role in its growth. Vandetanib, a multikinase inhibitor, suppresses the phosphorylation of VEGF receptor 2 (VEGFR-2) and EGF receptor (EGFR). The aim of this study was to clarify the antitumor effect of vandetanib in mouse HCCs.Experimental Design: We evaluated the effects of vandetanib on proliferation of human umbilical vein endothelial cells (HUVEC) and three hepatoma cell lines, as well as the phosphorylation of VEGFR-2 and EGFR in these cells. Mice were implanted with hepatoma cells subcutaneously or orthotopically in the liver and treated with 50 or 75 mg/kg vandetanib. We analyzed the effects of treatment on tumor cell proliferation and apoptosis, vessel density, phosphorylation of VEGFR-2 and EGFR, and production of VEGF, TGF-a, and EGF in tumor tissues. Adverse events on vandetanib administration were also investigated.Results: Vandetanib suppressed phosphorylation of VEGFR-2 in HUVECs and EGFR in hepatoma cells and inhibited cell proliferation. In tumor-bearing mice, vandetanib suppressed phosphorylation of VEGFR-2 and EGFR in tumor tissues, significantly reduced tumor vessel density, enhanced tumor cell apoptosis, suppressed tumor growth, improved survival, reduced number of intrahepatic metastases, and upregulated VEGF, TGF-a, and EGF in tumor tissues. Treatment with vandetanib was not associated with serious adverse events, including alanine aminotransferase abnormality, bone marrow suppression, or body weight loss.Conclusions: The antitumor effects of vandetanib in mice suggest that it is a potentially suitable and safe chemotherapeutic agent for HCCs.

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Section: Discussionmentioning

confidence: 99%

Vandetanib, an Inhibitor of VEGF Receptor-2 and EGF Receptor, Suppresses Tumor Development and Improves Prognosis of Liver Cancer in Mice

Inoue

Torimura

Nakamura

et al. 2012

Clinical Cancer Research

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“…Results of the mAb bevacizumab showed some activity in terms of stabilizing disease, but unfortunately, several major adverse effects have been reported, mostly related to gastrointestinal bleeding [63][64][65][66]. Other antiangiogenic multikinase inhibitors are currently being tested in early (cediranib, PI-88 and TSU-68) and advanced (brivanib and sunitinib) clinical investigations [67][68][69][70][71][72][73][74].…”

Section: Molecular Targeted Therapies For Hepatocellular Carcinomamentioning

confidence: 99%

Pathogenesis of hepatocellular carcinoma and molecular therapies

Mínguez¹,

Tovar²,

Chiang³

et al. 2009

Current Opinion in Gastroenterology

131

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“…Another VEGFR tyrosine kinase inhibitor, ZD6474 inhibits in vitro HCC cell proliferation and interferes with adhesion, migration, and invasion of HCC cells [15]. Additional evidence showing the importance of VEGFR inhibition was reported by Liu et al, who found that the multitargeted agent sorafenib inhibits cellular proliferation and induces apoptosis in HCC cell lines in vitro [16].…”

Section: Role Of Vegfr In Tumor Cell Proliferationmentioning

confidence: 93%