Use of an anti-viral drug, Ribavirin, as an anti-glioblastoma therapeutic View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2017-05

AUTHORS

F Volpin, J Casaos, J Sesen, A Mangraviti, J Choi, N Gorelick, J Frikeche, T Lott, R Felder, S J Scotland, T S K Eisinger-Mathason, H Brem, B Tyler, N Skuli

ABSTRACT

The median survival for glioblastoma patients is ~15 months despite aggressive surgery and radio-chemotherapy approaches. Thus, developing new therapeutics is necessary to improve the treatment of these invasive brain tumors, which are known to show high levels of the eukaryotic initiation factor, eIF4E, a potent oncogene. Ribavirin, the only clinically approved drug known to target eIF4E, is an anti-viral molecule currently used in hepatitis C treatment. Here, we report the effect of ribavirin on proliferation, cell cycle, cell death and migration of several human and murine glioma cell lines, as well as human glioblastoma stem-like cells, in vitro. In addition, we tested ribavirin efficacy in vivo, alone and in combination with temozolomide and radiation. Our work showed that ribavirin inhibits glioma cell growth and migration, and increases cell cycle arrest and cell death, potentially through modulation of the eIF4E, EZH2 and ERK pathways. We also demonstrate that ribavirin treatment in combination with temozolomide or irradiation increases cell death in glioma cells. Finally and most importantly, ribavirin treatment in vivo significantly enhances chemo-radiotherapy efficacy and improves survival of rats and mice orthotopically implanted with gliosarcoma tumors or glioma stem-like cells, respectively. On the basis of these results, we propose that ribavirin represents a new therapeutic option for glioblastoma patients as an enhancer of the cytotoxic effects of temozolomide and radiotherapy. More... »

PAGES

3037-3047

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/onc.2016.457

DOI

http://dx.doi.org/10.1038/onc.2016.457

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1009325029

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27941882


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