In vivo silencing of Reptin blocks the progression of human hepatocellular carcinoma in xenografts and is associated with replicative senescence.: Reptin silencing blocks liver cancer progression

Autor: Ménard, Ludovic, Taras, Danièle, Grigoletto, Aude, Haurie, Valérie, Nicou, Alexandra, Dugot-Senant, Nathalie, Costet, Pierre, Rousseau, Benoît, Rosenbaum, Jean
Přispěvatelé: Rosenbaum, Jean, Fibrose hépatique et cancer du foie, Université Bordeaux Segalen - Bordeaux 2-IFR66-Institut National de la Santé et de la Recherche Médicale (INSERM), Pathologies infectieuses et cancers : aspects biologiques et thérapeutiques (PICABT), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Animalerie spécialisée, Université Bordeaux Segalen - Bordeaux 2, Animalerie A2, Supported by grants to JR from Institut National du Cancer, Association pour la Recherche sur le Cancer, Agence Nationale pour la Recherche sur le SIDA et les Hépatites Virales, Ligue Nationale Contre le Cancer and Conseil Régional d'Aquitaine. VH was supported by a fellowship from Agence Nationale pour la Recherche sur le SIDA et les Hépatites Virales, and AN by a fellowship from Institut National du Cancer.
Jazyk: angličtina
Rok vydání: 2010
Předmět:
Zdroj: Journal of Hepatology
Journal of Hepatology, 2010, 52 (5), pp.681-9. ⟨10.1016/j.jhep.2009.12.029⟩
ISSN: 0168-8278
1600-0641
Popis: International audience; BACKGROUND & AIMS: We previously showed that Reptin is overexpressed in hepatocellular carcinoma (HCC), and that in vitro depletion of Reptin with siRNAs led to HCC cell growth arrest and apoptosis. Here, we asked whether in vivo targeting of Reptin in established tumours had a therapeutic effect. METHODS: We used lentiviral vectors to construct HuH7 and Hep3B cell lines with doxycycline (Dox)-dependent expression of Reptin (R2) or control shRNA (GL2). Cells were injected subcutaneously into immunodeficient mice, and Dox was given when tumours reached a volume of 250 mm(3). RESULTS: In vitro, the growth of GL2-Dox, GL2+Dox, and R2-Dox cells was undistinguishable whereas that of R2+Dox cells stopped 4 days after Dox treatment. The growth decrease was associated with increased apoptosis, and evidence of replicative senescence, as shown by staining for acid beta-galactosidase and the presence of senescence-associated heterochromatin foci. In xenografted mice, R2+Dox tumour growth stagnated or even regressed with prolonged treatment in contrast with the GL2-Dox, GL2+Dox, and R2-Dox tumours that progressed steadily. The blockage of tumour progression was associated with the induction of senescence and reduced cell proliferation. CONCLUSIONS: In vivo Reptin depletion leads to tumour growth arrest. Reptin may prove a valuable target in HCC.
Databáze: OpenAIRE
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