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In vivo restoration of RhoB expression leads to ovarian tumor regression

Cancer Gene Therapy volume 15, pages 456–464 (2008)Cite this article

Abstract

Ovarian cancers are very aggressive cancers most often diagnosed when metastasis has already occurred in the entire peritoneal cavity. Ovarian adenocarcinoma cells present an undetectable level of RhoB GTPase. Using preclinical ovarian cancer models, we aimed to evaluate the potential use of RhoB cDNA as a tumor suppressor gene in gene therapy. RhoB restoration in vitro, through recombinant adenovirus transduction, resulted in the apoptosis of endogenous RhoB protein low-expressing cell lines (OVCAR-3 and IGROV-1) through the activation of the intrinsic apoptotic caspase cascade. We showed that a single injection of 108 p.f.u. of adenoviral vector encoding a reporter gene into the peritoneal cavity of ovarian tumor bearing mice can induce the gene modification of a large quantity of cells throughout the cavity. We thereby tested the effect of AdRhoB injections to treat ovarian cancer-bearing mice. The ectopic expression of RhoB, following its introduction via viral transduction into nude mice in vivo, was highly effective in suppressing tumor growth of ovarian cancer xenografts. Therapeutic agents designed to correct defects of RhoB at the molecular level may thereby provide innovative treatment options for patients not responding to standard therapies.

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Abbreviations

Ad:

adenovirus

CMV:

cytomegalovirus

FCS:

fetal calf serum

GFP:

green fluorescent protein

MOI:

multiplicity of infection

OVCAR-3:

NIH-OVCAR3 cells

RhoB:

Ras homologous gene B

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Acknowledgements

The fluorescence imaging set up was partly supported by the IPA CNRS CEA program. We are grateful to Lourdes Gasquet and Christiane Pages at the animal facility. This study was supported by grants from The Region Midi Pyrénées, the GRICR (Groupe de Recherche Institut Claudius Regaud) and the University Toulouse III (France). Viral vectors have been produced in the Institut Claudius Regaud's vector core granted by the ‘ligue contre le cancer’.

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Authors and Affiliations

  1. INSERM U563, CPTP, Toulouse, France

    B Couderc, A Pradines, A Rafii, D Berg, M Penary & G Favre

  2. Institut Claudius Regaud, Toulouse, France

    B Couderc, A Pradines, A Rafii, D Berg, M Penary & G Favre

  3. Faculté des Sciences Pharmaceutiques, University Toulouse III, Toulouse, France

    B Couderc & G Favre

  4. EA3035, Institut Claudius Regaud, Toulouse, France

    B Couderc, A Deviers & C Allal

  5. UMR 5089 CNRS, IPBS, Toulouse, France

    M Golzio & J Teissie

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  1. B Couderc
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Correspondence to B Couderc.

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Couderc, B., Pradines, A., Rafii, A. et al. In vivo restoration of RhoB expression leads to ovarian tumor regression. Cancer Gene Ther 15, 456–464 (2008). https://doi.org/10.1038/cgt.2008.12

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  • DOI: https://doi.org/10.1038/cgt.2008.12

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