The growth-inhibitory effects of dexamethasone on renal cell carcinoma in vivo and in vitro.
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.
Arai
Yasuyuki
Y
Department of Urology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Nonomura
Norio
N
Nakai
Yasutomo
Y
Nishimura
Kazou
K
Oka
Daizo
D
Shiba
Masahiro
M
Nakayama
Masashi
M
Takayama
Hitoshi
H
Mizutani
Yoichi
Y
Miki
Tsuneharu
T
Okuyama
Akihiko
A
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
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