title: Sunitinib (SUTENT, SU11248) suppresses tumor growth and induces apoptosis in xenograft models of human hepatocellular carcinoma.
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 platelet-derived 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-beta 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.
authors.affiliation: Humphrey Oei Institute of Cancer Research, National Cancer Centre of Singapore, Singapore. cmrhth@nccs.com.sg
authors.forename: H
authors.initials: H
authors.lastname: Huynh
authors.forename: V C
authors.initials: VC
authors.lastname: Ngo
authors.forename: S P
authors.initials: SP
authors.lastname: Choo
authors.forename: D
authors.initials: D
authors.lastname: Poon
authors.forename: H N
authors.initials: HN
authors.lastname: Koong
authors.forename: C H
authors.initials: CH
authors.lastname: Thng
authors.forename: H C
authors.initials: HC
authors.lastname: Toh
authors.forename: L
authors.initials: L
authors.lastname: Zheng
authors.forename: L C
authors.initials: LC
authors.lastname: Ong
authors.forename: Y
authors.initials: Y
authors.lastname: Jin
authors.forename: I C
authors.initials: IC
authors.lastname: Song
authors.forename: A P C
authors.initials: AP
authors.lastname: Chang
authors.forename: H S
authors.initials: HS
authors.lastname: Ong
authors.forename: A Y F
authors.initials: AY
authors.lastname: Chung
authors.forename: P K H
authors.initials: PK
authors.lastname: Chow
authors.forename: K C
authors.initials: KC
authors.lastname: Soo
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D000068258:Bevacizumab; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D056945:Hep G2 Cells; D006801:Humans; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000188:drug therapy*; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy*; D051379:Mice; D016513:Mice, SCID; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D010766:Phosphorylation / Q000187:drug effects; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use*; D000077210:Sunitinib; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000068258:Bevacizumab; D000077210:Sunitinib