Inhibition of heme oxygenase 1 expression by small interfering RNA decreases orthotopic tumor growth in livers of mice.
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.
Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nuremberg, 91054 Erlangen, Germany. sass@pharmakologie.uni-erlangen.de
Gabriele
G
Sass
Petra
P
Leukel
Volker
V
Schmitz
Esther
E
Raskopf
Matthias
M
Ocker
Daniel
D
Neureiter
Matthias
M
Meissnitzer
Elena
E
Tasika
Andrea
A
Tannapfel
Gisa
G
Tiegs
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000201:enzymology*; D049109:Cell Proliferation; D015316:Genetic Therapy / Q000379:methods; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008113:Liver Neoplasms / Q000201:enzymology*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D051379:Mice; D034741:RNA, Small Interfering / Q000627:therapeutic use*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
D008565:Membrane Proteins; D034741:RNA, Small Interfering; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse