title: The heat shock protein 90 inhibitor SNX-2112 inhibits B16 melanoma cell             growth in vitro and in vivo.
abstract: SNX-2112 is a selective heat shock protein 90 (Hsp90) inhibitor which can             exert a potent anticancer activity. In this study, we investigated the effects             of SNX-2112 on B16 melanoma cells in vitro and in vivo. The 3-(4,5-dimetrylthiazol-2-yl)-2,             5-diphenyltetrazolium bromide (MTT) assay and flow cytometric analysis demonstrated             that SNX-2112 dose-dependently inhibited the growth of B16 cells, and induced             G0/G1 cell cycle arrest and apoptosis. Western blotting revealed that SNX-2112             lead to the degradation of Hsp90 client proteins including Akt, IKKα, NF-κB, B-Raf             and GSK3β. Furthermore, we assessed the antitumor effect of SNX-2112 in vivo,             using a xenograft model in C57BL/6 mice. Oral administration of SNX-2112 significantly             inhibited the growth of B16 tumors in mice, with a 47% inhibition observed at             dose of 80 mg/kg/day for 15 days, compared to control tumors. Hematoxylin-eosin             (H&E) staining of xenograft tissues showed that SNX-2112 also inhibited angiogenesis             and lead to a lower blood vessel density in the tumors, compared to the control             group. These findings demonstrate that SNX-2112 can exhibit a potent anticancer             activity against B16 melanoma cells both in vitro and in vivo, by inhibiting cell             proliferation and inducing cell cycle arrest and apoptosis in a mechanism dependent             on the degradation of Hsp90 client proteins.
authors.affiliation: Guangzhoujinan Biomedicine Research and Development Center, Guangdong Provincial Key Laboratory of Bioengineering Medicine, National Engineering Research Center of Genetic Medicine, Pharmacy College, Jinan University, Guangzhou 510632, PR China.
authors.forename: Kai-Sheng
authors.initials: KS
authors.lastname: Liu
authors.forename: Wei-Chao
authors.initials: WC
authors.lastname: Ding
authors.forename: Shao-Xiang
authors.initials: SX
authors.lastname: Wang
authors.forename: Zhong
authors.initials: Z
authors.lastname: Liu
authors.forename: Guo-Wen
authors.initials: GW
authors.lastname: Xing
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Yi-Fei
authors.initials: YF
authors.lastname: Wang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors; D000071679:Glycogen Synthase Kinase 3 beta; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology*; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D016328:NF-kappa B / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D018841:HSP90 Heat-Shock Proteins; D006576:Heterocyclic Compounds, 4 or More Rings; D016328:NF-kappa B; C534922:SNX 2112; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D051057:Proto-Oncogene Proteins c-akt; C496564:Chuk protein, mouse; D051550:I-kappa B Kinase; D020928:Mitogen-Activated Protein Kinases; D038362:Glycogen Synthase Kinase 3