Ochiai Yushi, Sumi Koichiro, Sano Emiko, Yoshimura Sodai, Yamamuro Shun, Ogino Akiyoshi, Ueda Takuya, Suzuki Yutaka, Nakayama Tomohiro, Hara Hiroyuki, Katayama Yoichi, Yoshino Atsuo
Department of Neurological Surgery, Nihon University School of Medicine, Tokyo 173-8610, Japan.
Department of Computational Biology and Medical Science, Graduate School of Frontier Sciences, The University of Tokyo, Chiba 277-8562, Japan.
Oncol Lett. 2020 Nov;20(5):178. doi: 10.3892/ol.2020.12039. Epub 2020 Aug 31.
The prognosis of gioblastoma, the standard chemotherapy agent for which is temozolomide (TMZ), remains poor despite recent advances in multimodal treatments. Therefore, it is necessary to identify and develop novel therapeutics for this malignant disease. Ribavirin, an anti-viral agent which is one of the standard agents for treatment of chronic hepatitis C in combination with interferon (IFN), was recently revealed to have an antitumor potential towards various tumor cells, including malignant glioma cells. The aim of the present study was to examine the antitumor effect of ribavirin in combination with TMZ and IFN-β on glioma cells and to evaluate the possibility that such combinations might represent a novel candidate for glioblastoma therapy. The combination of ribavirin with TMZ and IFN-β displayed a significant cell growth inhibitory effect with a ribavirin dose-dependency, including a relatively low concentration of ribavirin, on not only TMZ-sensitive but also TMZ-resistant malignant glioma cells. The antitumor efficacy of such a combination further indicated a synergistic interaction when assessed by the Chou-Talalay method. Furthermore, flow cytometry analysis suggested that apoptosis induction was one of the possible biological processes underlying the synergistic antitumor effect of these triple combination treatments. Therefore, such combinations may be potentially important in the clinical setting for glioblastoma treatment, although further detailed studies, e.g. on the adverse effects, are required.
胶质母细胞瘤的标准化疗药物是替莫唑胺（TMZ），尽管多模式治疗取得了最新进展，但其预后仍然很差。因此，有必要识别和开发针对这种恶性疾病的新型疗法。利巴韦林是一种抗病毒药物，是与干扰素（IFN）联合治疗慢性丙型肝炎的标准药物之一，最近发现它对包括恶性胶质瘤细胞在内的各种肿瘤细胞具有抗肿瘤潜力。本研究的目的是研究利巴韦林与TMZ和IFN-β联合对胶质瘤细胞的抗肿瘤作用，并评估这种联合可能成为胶质母细胞瘤治疗新候选方案的可能性。利巴韦林与TMZ和IFN-β的联合对不仅对TMZ敏感而且对TMZ耐药的恶性胶质瘤细胞显示出显著的细胞生长抑制作用，且具有利巴韦林剂量依赖性，包括相对较低浓度的利巴韦林。当通过Chou-Talalay方法评估时，这种联合的抗肿瘤功效进一步表明存在协同相互作用。此外，流式细胞术分析表明，诱导凋亡是这些三联联合治疗协同抗肿瘤作用的可能生物学过程之一。因此，尽管需要进一步进行详细研究，例如关于不良反应的研究，但这种联合在胶质母细胞瘤治疗的临床环境中可能具有潜在的重要意义。
