Inhibition of nuclear factor kappa B attenuates tumour progression in an animal model of renal cell carcinoma

Morais, Christudas, Healy, Helen, Johnson, David W. and Gobe, Glenda (2010) Inhibition of nuclear factor kappa B attenuates tumour progression in an animal model of renal cell carcinoma. Nephrology, Dialysis and Transplantation, 25 5: 1462-1473. doi:10.1093/ndt/gfp673


Author Morais, Christudas
Healy, Helen
Johnson, David W.
Gobe, Glenda
Title Inhibition of nuclear factor kappa B attenuates tumour progression in an animal model of renal cell carcinoma
Journal name Nephrology, Dialysis and Transplantation   Check publisher's open access policy
ISSN 0931-0509
1460-2385
Publication date 2010-05
Year available 2009
Sub-type Article (original research)
DOI 10.1093/ndt/gfp673
Volume 25
Issue 5
Start page 1462
End page 1473
Total pages 12
Editor N. Lameire
Place of publication United Kingdom
Publisher Oxford University Press
Collection year 2010
Language eng
Subject C1
920102 Cancer and Related Disorders
11 Medical and Health Sciences
Formatted abstract
Background. Renal cell carcinoma (RCC) is a highly metastatic and lethal disease with few efficacious treatments. Many studies have shown that the ubiquitous transcription factor nuclear factor kappa B (NF-κB) plays a key role in the
development and progression of many cancers including RCC. The aim of this investigation was to evaluate the anti-cancer effect of pyrrolidine dithiocarbamate (PDTC), a NF-κB inhibitor, in a murine xenograft model of RCC.
Methods. The metastatic human RCC cell line, SN12K1, was inoculated into the left kidneys of severe combined immunodeficiency mice and the effect of semi-continuous PDTC treatment (50mg/kg) on RCC growth analysed 5 weeks later. The analyses carried out in three groups (no treatment, RCC alone and RCC+PDTC) at 5weeks were: renal weight, protein expression by immunohistochemistry
and Western immunoblot, apoptosis (TdT-mediated nick end labelling and morphology) and mitosis (morphology).
Results. PDTCsignificantly decreasedRCCgrowth and the expression of NF-κB subunits (p50, p52, c-Rel and RelB), upstreamIKK-β and IKK-γ, but did not induce any changes in the expression of IκB-α and IκB-β. RCC growth was associated
with a significant decrease in the expression of the anti-apoptotic proteins Bcl-2 and Bcl-XL and increase in proapoptotic Bax, all of which were reversed by PDTC. Cell
proliferation was significantly reduced by PDTC.
Conclusion. The results demonstrate the potential anticancer benefits of treating NF-κB positive RCCs with NF-κB inhibitors like PDTC.
Keyword Apoptosis
NF-kappa B
Pyrrolidine dithiocarbamate
Renal Cell Carcinoma
Pyrrolidine dithiocarbamate
T-cells
Cancer-cells
Constitutive Activation
Induced Apoptosis
Bcl-2 Expression
Cystic-disease
Brain Ischemia
Nude-mice
Growth
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes # Received August 3, 2009. # Accepted November 16, 200

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
School of Medicine Publications
 
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Created: Fri, 16 Apr 2010, 16:31:49 EST by Fiona Mactaggart on behalf of Medicine - Princess Alexandra Hospital