title: The growth-inhibitory effects of dexamethasone on renal cell carcinoma in vivo and in vitro.
abstract: BACKGROUND
  Recently, several kinase inhibitors have been reported to exert stronger growth inhibitory effects on metastatic renal cell carcinomas (RCCs) than cytokines such as interferons (IFNs) and interleukin-2 (IL-2). On the contrary, the adverse effects of these drugs are also severe. The aim of this study is to analyze the growth-inhibitory effects of DEXamethasone (DEX) on RCC in vivo and in vitro.
  
  
  METHODS
  The MTT assay was performed using three RCC cell lines, OUR-10, Caki-1, and NC65. OUR-10 cells were subcutaneously transplanted to the dorsal area of nude mice. The nuclear translocation of glucocorticoid receptor (GR) and NF-kappa B was examined using appropriate antibodies. Concentrations of interleukin-6 (IL-6), IL-8, and vascular endothelial cell growth factor (VEGF) in the conditioned media and cytosol were measured by enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  All three RCC cell lines responded to DEX treatment. The growth of OUR-10 xenografts was significantly inhibited by administration of DEX. GR was translocated into the nucleus on DEX treatment. Intracellular IL-6, as well as IL-6 in the conditioned medium, decreased in OUR-10 cells following treatment with increasing amounts of DEX. Concentrations of IL-8 and VEGF in the conditioned medium of OUR-10 and NC65 cells also decreased following DEX treatment, with the inhibition of nuclear translocation of NF-kappa B.
  
  
  CONCLUSIONS
  DEX treatment is a candidate for advanced RCC therapy by inhibiting the activation of NF-kappa B and its downstream products such as IL-6, IL-8 and VEGF.
authors.affiliation: Department of Urology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Arai
authors.forename: Norio
authors.initials: N
authors.lastname: Nonomura
authors.forename: Yasutomo
authors.initials: Y
authors.lastname: Nakai
authors.forename: Kazou
authors.initials: K
authors.lastname: Nishimura
authors.forename: Daizo
authors.initials: D
authors.lastname: Oka
authors.forename: Masahiro
authors.initials: M
authors.lastname: Shiba
authors.forename: Masashi
authors.initials: M
authors.lastname: Nakayama
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takayama
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Mizutani
authors.forename: Tsuneharu
authors.initials: T
authors.lastname: Miki
authors.forename: Akihiko
authors.initials: A
authors.lastname: Okuyama
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D049109:Cell Proliferation / Q000187:drug effects*; D003907:Dexamethasone / Q000627:therapeutic use*; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000187:drug effects; D007680:Kidney Neoplasms / Q000188:drug therapy*; D051379:Mice; D008819:Mice, Nude; D016328:NF-kappa B / Q000187:drug effects; D009374:Neoplasms, Experimental / Q000188:drug therapy; D021381:Protein Transport / Q000187:drug effects; D011965:Receptors, Glucocorticoid / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D018931:Antineoplastic Agents, Hormonal; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D011965:Receptors, Glucocorticoid; D042461:Vascular Endothelial Growth Factor A; D003907:Dexamethasone