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Inhibition of heme oxygenase 1 expression by small interfering RNA decreases orthotopic tumor growth in livers of mice
Author(s) -
Sass Gabriele,
Leukel Petra,
Schmitz Volker,
Raskopf Esther,
Ocker Matthias,
Neureiter Daniel,
Meissnitzer Matthias,
Tasika Elena,
Tannapfel Andrea,
Tiegs Gisa
Publication year - 2008
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.23695
Subject(s) - gene knockdown , small interfering rna , cancer research , heme oxygenase , angiogenesis , apoptosis , cell growth , biology , hepatocellular carcinoma , cancer , tumor progression , rna interference , heme , rna , medicine , gene , enzyme , biochemistry
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. © 2008 Wiley‐Liss, Inc.