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Halofuginone suppresses the lung metastasis of chemically induced hepatocellular carcinoma in rats through MMP inhibition
Year:
2006
Source of publication :
Neoplasia
Authors :
Pines, Mark
;
.
Volume :
8
Co-Authors:
Taras, D., INSERM, E362, Bordeaux, F-33076, France, Université Victor Segalen Bordeaux 2, Bordeaux, F-33076, France, IFR 66, Bordeaux, F-33076, France
Blanc, J.-F., INSERM, E362, Bordeaux, F-33076, France, Université Victor Segalen Bordeaux 2, Bordeaux, F-33076, France, IFR 66, Bordeaux, F-33076, France
Rullier, A., INSERM, E362, Bordeaux, F-33076, France, Université Victor Segalen Bordeaux 2, Bordeaux, F-33076, France, IFR 66, Bordeaux, F-33076, France
Dugot-Senant, N., IFR 66, Bordeaux, F-33076, France
Laurendeau, I., Université Paris 5, UPRES EA 3618, Laboratoire de Génétique Moléculaire, Paris, F-75006, France
Bièche, I., Université Paris 5, UPRES EA 3618, Laboratoire de Génétique Moléculaire, Paris, F-75006, France
Pines, M., Institute of Animal Science, Volcani Center, Bet Dagan, Israel
Rosenbaum, J., INSERM, E362, Bordeaux, F-33076, France, Université Victor Segalen Bordeaux 2, Bordeaux, F-33076, France, IFR 66, Bordeaux, F-33076, France, GREF, INSERM E362, Université Victor Segalen, Bordeaux 2, Bordeaux, France
Facilitators :
From page:
312
To page:
318
(
Total pages:
7
)
Abstract:
Halofuginone, an inhibitor of collagen synthesis, appears to be a promising antitumoral drug in preclinical studies. We used a relevant rat model of autochthonous, chemically induced, spontaneously metastasizing hepatocellular carcinoma (HCC) to test the efficacy of halofuginone on tumor progression and matrix metalloproteinase (MMP) expression. Following sequential administration of diethylnitrosamine and N-nitrosomorpholine for 14 weeks, all animals developed HCC and then received halofuginone or its solvent for 10 weeks. The final number of liver tumors was lower in the halofuginone group than in the solvent group (57.2 ± 4.6 vs 68 ± 5.0; P < .01). The percentage of the lung surface infiltrated by metastasis was much smaller in the halofuginone group (0.3 ± 0.2%) than in the solvent group (13.5 ± 10.1%; P < .02). MMP-9 activity was decreased in the halofuginone group by 89% and 63% in non-neoplastic parts of the liver and tumor, respectively. The percentage of active MMP-2 was reduced by 90% in non-neoplastic parts of the liver and by 61% in tumors. This was likely subsequent to a decreased expression of both MMP-14 and tissue inhibitor of matrix metalloproteinase-2, which are required for pro-MMP-2 activation. These results, obtained from a clinically relevant model, further suggest the potential benefit of halofuginone in HCC. Copyright © 2006 Neoplasia Press, Inc. All rights reserved.
Note:
Related Files :
animal experiment
animal model
Animals
animal tissue
diethylnitrosamine
drug effect
Male
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More details
DOI :
10.1593/neo.05796
Article number:
Affiliations:
Database:
Scopus
Publication Type:
article
;
.
Language:
English
Editors' remarks:
ID:
19287
Last updated date:
02/03/2022 17:27
Creation date:
16/04/2018 23:27
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Scientific Publication
Halofuginone suppresses the lung metastasis of chemically induced hepatocellular carcinoma in rats through MMP inhibition
8
Taras, D., INSERM, E362, Bordeaux, F-33076, France, Université Victor Segalen Bordeaux 2, Bordeaux, F-33076, France, IFR 66, Bordeaux, F-33076, France
Blanc, J.-F., INSERM, E362, Bordeaux, F-33076, France, Université Victor Segalen Bordeaux 2, Bordeaux, F-33076, France, IFR 66, Bordeaux, F-33076, France
Rullier, A., INSERM, E362, Bordeaux, F-33076, France, Université Victor Segalen Bordeaux 2, Bordeaux, F-33076, France, IFR 66, Bordeaux, F-33076, France
Dugot-Senant, N., IFR 66, Bordeaux, F-33076, France
Laurendeau, I., Université Paris 5, UPRES EA 3618, Laboratoire de Génétique Moléculaire, Paris, F-75006, France
Bièche, I., Université Paris 5, UPRES EA 3618, Laboratoire de Génétique Moléculaire, Paris, F-75006, France
Pines, M., Institute of Animal Science, Volcani Center, Bet Dagan, Israel
Rosenbaum, J., INSERM, E362, Bordeaux, F-33076, France, Université Victor Segalen Bordeaux 2, Bordeaux, F-33076, France, IFR 66, Bordeaux, F-33076, France, GREF, INSERM E362, Université Victor Segalen, Bordeaux 2, Bordeaux, France
Halofuginone suppresses the lung metastasis of chemically induced hepatocellular carcinoma in rats through MMP inhibition
Halofuginone, an inhibitor of collagen synthesis, appears to be a promising antitumoral drug in preclinical studies. We used a relevant rat model of autochthonous, chemically induced, spontaneously metastasizing hepatocellular carcinoma (HCC) to test the efficacy of halofuginone on tumor progression and matrix metalloproteinase (MMP) expression. Following sequential administration of diethylnitrosamine and N-nitrosomorpholine for 14 weeks, all animals developed HCC and then received halofuginone or its solvent for 10 weeks. The final number of liver tumors was lower in the halofuginone group than in the solvent group (57.2 ± 4.6 vs 68 ± 5.0; P < .01). The percentage of the lung surface infiltrated by metastasis was much smaller in the halofuginone group (0.3 ± 0.2%) than in the solvent group (13.5 ± 10.1%; P < .02). MMP-9 activity was decreased in the halofuginone group by 89% and 63% in non-neoplastic parts of the liver and tumor, respectively. The percentage of active MMP-2 was reduced by 90% in non-neoplastic parts of the liver and by 61% in tumors. This was likely subsequent to a decreased expression of both MMP-14 and tissue inhibitor of matrix metalloproteinase-2, which are required for pro-MMP-2 activation. These results, obtained from a clinically relevant model, further suggest the potential benefit of halofuginone in HCC. Copyright © 2006 Neoplasia Press, Inc. All rights reserved.
Scientific Publication
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