Abstract
Hepatocellular carcinoma (HCC) is the fifth most common and third deadliest primary neoplasm. Since HCC is a particularly vascular solid tumor, we determined the antitumor and antiangiogenic activities of sunitinib malate, a potent inhibitor of two receptors involved in angiogenesis – vascular endothelial growth factor receptor (VEGFR) and plateletderived growth factor receptor (PDGFR). In the present study, we reported that treatment of HepG2 and SK-Hep-1 cells with sunitinib led to growth inhibition and apoptosis in a dose-dependent fashion. Sunitinib inhibited phosphorylation of VEGFR-2 at Tyr951 and PDGFR-β at Tyr1021 both in vitro and in vivo. Sunitinib also suppressed tumor growth of five patient-derived xenografts. Sunitinib-induced tumor growth inhibition was associated with increased apoptosis, reduced microvessel density and inhibition of cell proliferation. This study provides a strong rationale for further clinical investigation of sunitinib in patients with hepatocellular carcinoma.
Keywords: Sunitinib, hepatocellular carcinoma, growth inhibition, anti-angiogenesis
Current Cancer Drug Targets
Title: Sunitinib (SUTENT, SU11248) Suppresses Tumor Growth and Induces Apoptosis in Xenograft Models of Human Hepatocellular Carcinoma
Volume: 9 Issue: 6
Author(s): H. Huynh, V. C. Ngo, S. P. Choo, D. Poon, H. N. Koong, C. H. Thng, H. C. Toh, L. Zheng, L. C. Ong, Y. Jin, I. C. Song, A. P.C. Chang, H. S. Ong, A. Y.F. Chung, P. K.H. Chow and K. C. Soo
Affiliation:
Keywords: Sunitinib, hepatocellular carcinoma, growth inhibition, anti-angiogenesis
Abstract: Hepatocellular carcinoma (HCC) is the fifth most common and third deadliest primary neoplasm. Since HCC is a particularly vascular solid tumor, we determined the antitumor and antiangiogenic activities of sunitinib malate, a potent inhibitor of two receptors involved in angiogenesis – vascular endothelial growth factor receptor (VEGFR) and plateletderived growth factor receptor (PDGFR). In the present study, we reported that treatment of HepG2 and SK-Hep-1 cells with sunitinib led to growth inhibition and apoptosis in a dose-dependent fashion. Sunitinib inhibited phosphorylation of VEGFR-2 at Tyr951 and PDGFR-β at Tyr1021 both in vitro and in vivo. Sunitinib also suppressed tumor growth of five patient-derived xenografts. Sunitinib-induced tumor growth inhibition was associated with increased apoptosis, reduced microvessel density and inhibition of cell proliferation. This study provides a strong rationale for further clinical investigation of sunitinib in patients with hepatocellular carcinoma.
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Cite this article as:
Huynh H., Ngo C. V., Choo P. S., Poon D., Koong N. H., Thng H. C., Toh C. H., Zheng L., Ong C. L., Jin Y., Song C. I., Chang P.C. A., Ong S. H., Chung Y.F. A., Chow K.H. P. and Soo C. K., Sunitinib (SUTENT, SU11248) Suppresses Tumor Growth and Induces Apoptosis in Xenograft Models of Human Hepatocellular Carcinoma, Current Cancer Drug Targets 2009; 9 (6) . https://dx.doi.org/10.2174/156800909789271530
DOI https://dx.doi.org/10.2174/156800909789271530 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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