Inhibition of Rho pathways induces radiosensitization and oxygenation in human glioblastoma xenografts View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2003-12

AUTHORS

Isabelle Ader, Caroline Delmas, Jacques Bonnet, Philippe Rochaix, Gilles Favre, Christine Toulas, Elizabeth Cohen-Jonathan-Moyal

ABSTRACT

We previously demonstrated in vitro that inhibiting the biological pathways of the small GTPase Rho radiosensitizes the human glioma U87 cell line. The aim of this study was to determine if Rho might be involved in the control of in vivo radiosensitivity altogether by controlling cellular radioresistance and by modifying tumor microenvironment. We demonstrate here that the in vivo induction of the dominant negative of Rho, RhoBN19, in U87 xenografts induces a significant decrease of tumor cell survival after irradiation more important than the one we previously observed in vitro. This in vivo increased effect of RhoBN19 expression is due to the improvement of the tumor oxygenation associated with a significant decrease of the vessel density and of the metalloproteinase 2 (MMP2) expression. Moreover, in vitro RhoBN19 expression in U87 cells leads to the inhibition of MMP2 activity. Our results demonstrate for the first time that inhibiting Rho pathways modifies the in vivo radiosensitivity of human glioma cells by controlling intrinsic radioresistance, hypoxia and angiogenesis. These data strongly suggest that Rho should be a major determinant of cellular resistance to ionizing radiation. More... »

PAGES

1207095

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.onc.1207095

DOI

http://dx.doi.org/10.1038/sj.onc.1207095

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1028434217

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/14654782


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