Sunitinib (SUTENT, SU11248) Suppresses Tumor Growth and Induces Apoptosis in Xenograft Models of Human Hepatocellular Carcinoma

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 , K. C. Soo .

Journal Name: Current Cancer Drug Targets

Volume 9 , Issue 6 , 2009

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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

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Article Details

VOLUME: 9
ISSUE: 6
Year: 2009
Page: [738 - 747]
Pages: 10
DOI: 10.2174/156800909789271530
Price: $58

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