title: Efficacy of ribavirin against malignant glioma cell lines.
abstract: Ribavirin (1-β-D-ribofuranosy-1,2,4-triazole-3-carboxamide) has been widely administered as an antiviral agent against RNA and DNA viruses. Ribavirin, in combination with interferon, has predominantly been applied in the treatment of the hepatitis C virus infection and its potential antitumor efficacy has recently become a point of interest. The aim of the present study was to evaluate the effect of ribavirin on the growth of malignant glioma cells, to identify novel predictive genes in malignant glioma cells (by analyzing gene expression profiles) and to assess the influence of ribavirin on the cell cycle of malignant glioma cells. The present study evaluated the antitumor efficacy of ribavirin against various malignant glioma cell lines (A-172, AM-38, T98G, U-87MG, U-138MG, U-251MG and YH-13). After culturing the cells in ribavirin-containing culture medium (final concentration, 0-1,000 μM) for 72 h, the viable proliferated cells were harvested and counted. The half maximal inhibitory concentration of ribavirin, with regard to the growth of the malignant glioma cell lines, was determined from the concentration of ribavirin required for 50% growth inhibition in comparison to the untreated control cells. Furthermore, the current study identified the genes in which the gene expression levels correlated with the ribavirin sensitivity of the malignant glioma cells lines, using a high-density oligonucleotide array. Finally, cell cycle analysis was performed on the U-87MG cell line. It was identified that ribavirin inhibited the growth of all of the malignant glioma cell lines in a dose-dependent manner, although the ribavirin sensitivity varied between each cell line. Of the extracted genes,PDGFRAdemonstrated the strongest positive correlation between gene expression level and ribavirin sensitivity. Cell cycle analysis of the U-87MG cell line demonstrated that ribavirin treatment induces G0/G1 arrest and thus may be an effective agent for inhibiting malignant glioma cell growth. Therefore, the results of the current study indicate that ribavirin may have potential as a therapeutic agent in the treatment of malignant gliomas.
authors.affiliation: Department of Neurological Surgery, Nihon University School of Medicine, Tokyo 173-8610, Japan.
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Ogino
authors.affiliation: Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba 277-8562, Japan.
authors.forename: Emiko
authors.initials: E
authors.lastname: Sano
authors.affiliation: Department of Neurological Surgery, Nihon University School of Medicine, Tokyo 173-8610, Japan.
authors.forename: Yushi
authors.initials: Y
authors.lastname: Ochiai
authors.affiliation: Department of Neurological Surgery, Nihon University School of Medicine, Tokyo 173-8610, Japan.
authors.forename: Shun
authors.initials: S
authors.lastname: Yamamuro
authors.affiliation: Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba 277-8562, Japan ; Medical Proteomics Laboratory, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Tashiro
authors.affiliation: Department of Neurological Surgery, Nihon University School of Medicine, Tokyo 173-8610, Japan.
authors.forename: Kazunari
authors.initials: K
authors.lastname: Yachi
authors.affiliation: Department of Neurological Surgery, Nihon University School of Medicine, Tokyo 173-8610, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ohta
authors.affiliation: Department of Neurological Surgery, Nihon University School of Medicine, Tokyo 173-8610, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Fukushima
authors.affiliation: New Energy and Industrial Technology Development Organization, Kawasaki 212-8554, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Okamoto
authors.affiliation: Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba 277-8562, Japan ; Medical Proteomics Laboratory, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Kouhei
authors.initials: K
authors.lastname: Tsumoto
authors.affiliation: Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba 277-8562, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Ueda
authors.affiliation: Department of Neurological Surgery, Nihon University School of Medicine, Tokyo 173-8610, Japan.
authors.forename: Atsuo
authors.initials: A
authors.lastname: Yoshino
authors.affiliation: Department of Neurological Surgery, Nihon University School of Medicine, Tokyo 173-8610, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Katayama
keywords: malignant glioma; ribavirin