title: [HSP90 Inhibitor 17-AAG Inhibits Multiple Myeloma Cell Proliferation by Down-regulating Wnt/β-Catenin Signaling Pathway].
abstract: OBJECTIVE
  To investigate the inhibitory effect of HSP90 inhibitory 17-AAG on proliferation of multiple myeloma cells and its main mechanism.
  
  
  METHODS
  The multiple myeloma cells U266 were treated with 17-AAG of different concentrations (200, 400, 600 and 800 nmol/L) for 24, 48, and 72 hours respectively, then the proliferation rate, expression levels of β-catenin and C-MYC protein, as well as cell cycle of U266 cells were treated with 17-AAG and were detected by MTT method, Western blot and flow cytometry, respectively.
  
  
  RESULTS
  The 17-AAG showed inhibitory effect on the proliferation of U266 cells in dose- and time-depetent manners (r = -0.518, P < 0.05 and r = -0.473, P < 0.05), while the culture medium without 17-AAG displayed no inhibitory effect on proliferation of U266 cells (P > 0.05). The result of culturing U266 cells for 72 hours by 17-AAG of different concentrations showed that the more high of 17-AAG concentration, the more low level of β-catenin and C-MYC proteins (P < 0.05); At same time of culture, the more high of 17-AAG concentration, the more high of cell ratio in G1 phase (P < 0.05), at same concentration of 17-AAG, the more long time of culture, the more high of cell ratio in G1 phase (P < 0.05).
  
  
  CONCLUSIONS
  The HSP90 inhibitory 17-AAG can inhibit the proliferation of multiple myeloma cells, the down-regulation of Wnt/β-catenin signaling pathway and inhibition of HSP90 expression may be the main mechnisms of 17-AAG effect.
authors.affiliation: Department of Hematology, Department of Statisties, Huaian First Hospital Affiliated to Nanjing Medical University, Huaian 223300, Jiangsu Province, China. E-mail: 21347725@qq.com.
authors.forename: Kan-Kan
authors.initials: KK
authors.lastname: Chen
authors.affiliation: Department of Hematology, Department of Statisties, Huaian First Hospital Affiliated to Nanjing Medical University, Huaian 223300, Jiangsu Province, China.
authors.forename: Zheng-Mei
authors.initials: ZM
authors.lastname: He
authors.affiliation: Department of Hematology, Department of Statisties, Huaian First Hospital Affiliated to Nanjing Medical University, Huaian 223300, Jiangsu Province, China.
authors.forename: Bang-He
authors.initials: BH
authors.lastname: Ding
authors.affiliation: Department of Hematology, Department of Statisties, Huaian First Hospital Affiliated to Nanjing Medical University, Huaian 223300, Jiangsu Province, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Hematology, Department of Statisties, Huaian First Hospital Affiliated to Nanjing Medical University, Huaian 223300, Jiangsu Province, China.
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Zhang
authors.affiliation: Department of Hematology, Department of Statisties, Huaian First Hospital Affiliated to Nanjing Medical University, Huaian 223300, Jiangsu Province, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Yu
authors.forename: Jian
authors.initials: J
authors.lastname: Gao
mesh_terms: D017209:Apoptosis; D016227:Benzoquinones / Q000494:pharmacology*; D002453:Cell Cycle; D002455:Cell Division; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D047029:Lactams, Macrocyclic / Q000494:pharmacology*; D009101:Multiple Myeloma / Q000378:metabolism / Q000473:pathology*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D016227:Benzoquinones; C495270:CTNNB1 protein, human; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D016271:Proto-Oncogene Proteins c-myc; D051176:beta Catenin; C112765:tanespimycin