In vivo restoration of RhoB expression leads to ovarian tumor regression

B. Couderc, A. Pradines, A. Rafii, M. Golzio, A. Deviers, C. Allal, D. Berg, M. Penary, J. Teissie, G. Favre

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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.

Original languageEnglish
Pages (from-to)456-464
Number of pages9
JournalCancer Gene Therapy
Volume15
Issue number7
DOIs
Publication statusPublished - 14 Jul 2008

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Keywords

  • Adenovirus vector
  • Apoptosis
  • Ovarian adenocarcinoma cells
  • RhoB GTPase
  • Tumor growth

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cancer Research

Cite this

Couderc, B., Pradines, A., Rafii, A., Golzio, M., Deviers, A., Allal, C., Berg, D., Penary, M., Teissie, J., & Favre, G. (2008). In vivo restoration of RhoB expression leads to ovarian tumor regression. Cancer Gene Therapy, 15(7), 456-464. https://doi.org/10.1038/cgt.2008.12