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

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.

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