title: Secreted clusterin (sCLU) regulates cell proliferation and chemosensitivity to cisplatin by modulating ERK1/2 signals in human osteosarcoma cells.
abstract: BACKGROUND
  Several studies have shown that secreted clusterin (sCLU) up-regulation in multi-drug resistant osteosarcoma (OS) cells relates to enhanced drug resistance. Furthermore, sCLU silencing directed against sCLU induces significant reduction of cellular growth and sensitizes OS cells to chemotherapy. However, the molecular mechanisms underlying the effect of sCLU on OS cells are not known.
  
  
  METHODS
  To evaluate the roles and possible mechanisms of sCLU in chemoresistance of OS cells to cisplatin (DPP), we utilized RNA interference to knockdown sCLU expression in the sCLU-rich U-2 OS cells and to overexpress sCLU in the sCLU-poorer KH OS cells, and further assessed the cell viability and chemosensitivity to DDP as well as possible signaling transduction pathways.
  
  
  RESULTS
  The data showed that sCLU depletion inhibited growth and sensitized sCLU-rich U-2 OS cells to cisplatin in vitro and in vivo by inducing inactivation of ERK1/2, and sCLU overexpression promoted growth and increased resistance of sCLU-less KH OS cells to cisplatin in vitro and in vivo by activation of ERK1/2.
  
  
  CONCLUSIONS
  The data also suggests critical roles of sCLU in OS cell chemoresistance to DPP and raises the possibility of sCLU depletion as a promising approach to OS therapy.
authors.forename: Hai
authors.initials: H
authors.lastname: Huang
authors.forename: Linna
authors.initials: L
authors.lastname: Wang
authors.forename: Mingyu
authors.initials: M
authors.lastname: Li
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, the Affiliated Hospital of QingDao University, QinDao 266003, China. zhanglinmzs@126.com.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects*; D002945:Cisplatin / Q000494:pharmacology*; D051152:Clusterin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D012516:Osteosarcoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C495242:CLU protein, human; D051152:Clusterin; D034741:RNA, Small Interfering; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D002945:Cisplatin
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