Inhibition of heme oxygenase 1 expression by small interfering RNA decreases orthotopic tumor growth in livers of mice

被引：91

作者：

Sass, Gabriele ^{[1
]}

Leukel, Petra ^{[1
]}

Schmitz, Volker ^{[2
]}

Raskopf, Esther ^{[2
]}

Ocker, Matthias ^{[3
]}

Neureiter, Daniel ^{[4
]}

Meissnitzer, Matthias ^{[4
]}

Tasika, Elena ^{[1
]}

Tannapfel, Andrea ^{[5
]}

Tiegs, Gisa ^{[1
,6
]}

机构：

[1] Univ Erlangen Nurnberg, Inst Expt & Clin Pharmacol & Toxicol, D-91054 Erlangen, Germany

[2] Univ Hosp Bonn, Dept Internal Med 1, D-53105 Bonn, Germany

[3] Univ Hosp Erlangen, Dept Med 1, D-91054 Erlangen, Germany

[4] Paracelsus Private Med Univ, Salzburger Landeskliniken, Inst Pathol, Salzburg, Austria

[5] Ruhr Univ Bochum, Inst Pathol, D-44780 Bochum, Germany

[6] Univ Med Ctr Hamburg Eppendorf, Ctr Internal Med, Div Exp Immunol & Hepatol, Hamburg, Germany

来源：

INTERNATIONAL JOURNAL OF CANCER | 2008年 / 123卷 / 06期

关键词：

antiapoptotic protein; HCC; small interfering RNA; HO-1;

D O I：

10.1002/ijc.23695

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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. (C) 2008 Wiley-Liss, Inc.

引用

页码：1269 / 1277

页数：9

共 47 条

[1] Upregulation of heme oxygenase-1 protects genetically fat Zucker rat livers from ischemia/reperfusion injury [J].

Amersi, F ;

Buelow, R ;

Kato, H ;

Ke, BB ;

Coito, AJ ;

Shen, XD ;

Zhao, DL ;

Zaky, J ;

Melinek, J ;

Lassman, CR ;

Kolls, JK ;

Alam, J ;

Ritter, T ;

Volk, HD ;

Farmer, DG ;

Ghobrial, RM ;

Busuttil, RW ;

Kupiec-Weglinski, JW .

JOURNAL OF CLINICAL INVESTIGATION, 1999, 104 (11) :1631-1639

[2] Expression pattern of heme oxygenase isoenzymes 1 and 2 in normal and stress-exposed rat liver [J].

Bauer, I ;

Wanner, GA ;

Rensing, H ;

Alte, G ;

Miescher, EA ;

Wolf, B ;

Pannen, BHJ ;

Clemens, MG ;

Bauer, M .

HEPATOLOGY, 1998, 27 (03) :829-838

[3]

Bergmeyer H.U., 1984, METHOD ENZYMAT AN, P416

[4] Carbon monoxide generated by heme oxygenase 1 suppresses endothelial cell apoptosis [J].

Brouard, S ;

Otterbein, LE ;

Anrather, J ;

Tobiasch, E ;

Bach, FH ;

Choi, AMK ;

Soares, MP .

JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 192 (07) :1015-1025

[5] Immunohistochemical analysis of heme oxygenase-1 in preneoplastic and neoplastic lesions during chemical hepatocarcinogenesis [J].

Caballero, F ;

Meiss, R ;

Gimenez, A ;

Batlle, A ;

Vazquez, E .

INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, 2004, 85 (04) :213-221

[6] INTERLEUKIN-1 AND TUMOR-NECROSIS-FACTOR INDUCE HEPATIC HEME OXYGENASE - FEEDBACK-REGULATION BY GLUCOCORTICOIDS [J].

CANTONI, L ;

ROSSI, C ;

RIZZARDINI, M ;

GADINA, M ;

GHEZZI, P .

BIOCHEMICAL JOURNAL, 1991, 279 :891-894

[7]

DARLINGTON GJ, 1980, J NATL CANCER I, V64, P809

[8] Projecting future complications of chronic hepatitis C in the United States [J].

Davis, GL ;

Albright, JE ;

Cook, SF ;

Rosenberg, DM .

LIVER TRANSPLANTATION, 2003, 9 (04) :331-338

[9] Induction of haem oxygenase-1 by nitric oxide and ischaemia in experimental solid tumours and implications for tumour growth [J].

Doi, K ;

Akaike, T ;

Fujii, S ;

Tanaka, S ;

Ikebe, N ;

Beppu, T ;

Shibahara, S ;

Ogawa, M ;

Maeda, H .

BRITISH JOURNAL OF CANCER, 1999, 80 (12) :1945-1954

[10] Enhancement of chemotherapeutic response of tumor cells by a heme oxygenase inhibitor, pegylated zinc protoporphyrin [J].

Fang, J ;

Sawa, T ;

Akaike, T ;

Greish, K ;

Maeda, H .

INTERNATIONAL JOURNAL OF CANCER, 2004, 109 (01) :1-8

← 1 2 3 4 5 →