Document Detail

Inhibition of heme oxygenase 1 expression by small interfering RNA decreases orthotopic tumor growth in livers of mice.
MedLine Citation:
PMID:  18566988     Owner:  NLM     Status:  MEDLINE    
Endogenous overexpression of the antiapoptotic protein heme oxygenase 1 (HO-1) has been shown to occur in various cancer diseases and might contribute to cancer progression. We compared the expression levels of HO-1 in human liver to expression levels in hepatocellular carcinoma (HCC), as well as the effect of HO-1 inhibition by small interfering RNA (siRNA) on cellular survival and apoptosis in the mouse hepatoma cell lines Hepa129 and Hepa1-6 and on orthotopic tumor growth in immune-competent C3H/HeN mice. Our results show that HO-1 is frequently overexpressed in human HCC. Downmodulation of HO-1 by siRNA resulted in increased cellular damage and apoptosis, reduced proliferation, reduced growth of orthotopic HCC and reduced angiogenesis. Livers and kidneys of treated animals did not reveal signs of damage by this treatment. In conclusion, a specific knockdown of HO-1 might represent a novel therapeutic approach in HCC therapy.
Gabriele Sass; Petra Leukel; Volker Schmitz; Esther Raskopf; Matthias Ocker; Daniel Neureiter; Matthias Meissnitzer; Elena Tasika; Andrea Tannapfel; Gisa Tiegs
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  123     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-07-23     Completed Date:  2008-08-22     Revised Date:  2009-07-06    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1269-77     Citation Subset:  IM    
Copyright Information:
Copyright 2008 Wiley-Liss, Inc.
Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nuremberg, 91054 Erlangen, Germany.
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MeSH Terms
Apoptosis / physiology
Blotting, Western
Carcinoma, Hepatocellular / enzymology*
Cell Proliferation
Gene Therapy / methods
Heme Oxygenase-1 / antagonists & inhibitors,  biosynthesis*
In Situ Nick-End Labeling
Liver Neoplasms / enzymology*
Membrane Proteins / antagonists & inhibitors,  biosynthesis*
RNA, Small Interfering / therapeutic use*
Reverse Transcriptase Polymerase Chain Reaction
Xenograft Model Antitumor Assays
Reg. No./Substance:
0/Membrane Proteins; 0/RNA, Small Interfering; EC Oxygenase-1; EC protein, mouse
Comment In:
Int J Cancer. 2009 Aug 1;125(3):736   [PMID:  19415748 ]

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