title: HSP27 expression levels are associated with the sensitivity of hepatocellular carcinoma cells to 17-allylamino-17-demethoxygeldanamycin.
abstract: AIMS, MATERIALS & METHODS: As heat-shock proteins are associated with tumor proliferation, differentiation, invasion and metastasis, we investigated whether targeting Hsp90 with the geldanamycin derivative 17-allylamino-17-demethoxygeldanamycin (17AAG) can inhibit the viability of hepatocellular carcinoma cell lines with various levels of metastatic potential. In addition, we investigated whether the use of Hsp27-siRNA can decrease resistance to 17AAG.
  
  
  RESULTS
  Although 17AAG upregulated the expression of heat-shock proteins, it did not affect the expression of Hsp90 client proteins in normal hepatocytes. Hsp90 inhibition by 17AAG degraded its client proteins in both low- and high-metastatic potential cell lines. siRNA inhibited Hsp27 expression in cell lines and improved the sensitivity of 17AAG.
  
  
  CONCLUSIONS
  17AAG inhibited the viability of hepatocellular carcinoma cells by degrading Hsp90 client proteins. The sensitivity of cells to 17AAG is associated with the level of Hsp27 expression.
authors.affiliation: Medical Oncology Department, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Yuehong
authors.initials: Y
authors.lastname: Cui
authors.forename: Weizhong
authors.initials: W
authors.lastname: Wu
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Zhou
authors.forename: Qian
authors.initials: Q
authors.lastname: Xie
authors.forename: Tianshu
authors.initials: T
authors.lastname: Liu
authors.forename: Jianjun
authors.initials: J
authors.lastname: Jin
authors.forename: Kangda
authors.initials: K
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D016227:Benzoquinones / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins; D056945:Hep G2 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D047029:Lactams, Macrocyclic / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D018832:Molecular Chaperones; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D016227:Benzoquinones; D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D018832:Molecular Chaperones; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D034741:RNA, Small Interfering; C057725:HSPB1 protein, human; C112765:tanespimycin