Ribavirin as a potential therapeutic for atypical teratoid/rhabdoid tumors.
Ribavirin as a potential therapeutic for atypical teratoid/rhabdoid tumors.
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DOI：
10.18632/oncotarget.23883
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发表时间：
2018-01-30
期刊：
影响因子：
--
通讯作者：
Skuli N
中科院分区：
文献类型：
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作者：
Casaos J;Huq S;Lott T;Felder R;Choi J;Gorelick N;Peters M;Xia Y;Maxwell R;Zhao T;Ji C;Simon T;Sesen J;Scotland SJ;Kast RE;Rubens J;Raabe E;Eberhart CG;Jackson EM;Brem H;Tyler B;Skuli N
非典型畸胎样/横纹肌样肿瘤（AT/RT）是高度侵袭性的恶性肿瘤，是6个月以下儿童最常见的恶性脑肿瘤。目前，AT/RT还没有标准的治疗方法。最近的研究报告了利巴韦林的潜在抗肿瘤特性，利巴韦林是一种鸟苷类似物和抗病毒分子，经食品和药物管理局批准用于治疗丙型肝炎。我们以前证明利巴韦林抑制胶质瘤细胞生长在体外和体内。基于这些结果和不存在利巴韦林在AT/RT中的临床前模型的事实，我们决定在体外和体内研究利巴韦林对几种人AT/RT细胞系（BT 12、BT 16和BT37）的作用。我们提供的证据表明，利巴韦林对AT/RT细胞生长有显着影响，并增加细胞周期阻滞和细胞死亡，可能通过调节eIF 4 E和/或EZH 2途径。有趣的是，使用划痕和transwell Boyden室测定，我们观察到利巴韦林也损害AT/RT细胞迁移，侵袭和粘附。最后，我们证明利巴韦林显着提高原位植入BT 12细胞的小鼠的存活率。我们的研究证实，利巴韦林通过减少肿瘤细胞的生长和扩散，对AT/RT有效，并可能为患有这种致命疾病的儿童提供一种新的治疗选择。
Atypical teratoid/rhabdoid tumors (AT/RT) are highly aggressive, malignant tumors and are the most common malignant brain tumor in children under 6 months of age. Currently, there is no standard treatment for AT/RT. Recent studies have reported potential anti-tumoral properties of ribavirin, a guanosine analog and anti-viral molecule approved by the Food and Drug Administration for treatment of hepatitis C. We previously demonstrated that ribavirin inhibited glioma cell growth in vitro and in vivo. Based on these results and the fact that no pre-clinical model of ribavirin in AT/RT exists, we decided to investigate the effect of ribavirin on several human AT/RT cell lines (BT12, BT16, and BT37) both in vitro and in vivo. We provide evidence that ribavirin has a significant impact on AT/RT cell growth and increases cell cycle arrest and cell death, potentially through modulation of the eIF4E and/or EZH2 pathways. Interestingly, using scratch wound and transwell Boyden chamber assays, we observed that ribavirin also impairs AT/RT cell migration, invasion, and adhesion. Finally, we demonstrate that ribavirin significantly improves the survival of mice orthotopically implanted with BT12 cells. Our work establishes that ribavirin is effective against AT/RT by decreasing tumoral cell growth and dissemination and could represent a new therapeutic option for children with this deadly disease.