Kerl Kornelius, Moreno Natalia, Holsten Till, Ahlfeld Julia, Mertins Julius, Hotfilder Marc, Kool Marcel, Bartelheim Kerstin, Schleicher Sabine, Handgretinger Rupert, Schüller Ulrich, Meisterernst Michael, Frühwald Michael C
Institute of Molecular Tumor Biology, Westfalian Wilhelms University, Muenster, Germany; Department of Pediatric Hematology and Oncology, University Children's Hospital Muenster, Muenster, Germany.
Int J Cancer. 2014 Aug 15;135(4):989-95. doi: 10.1002/ijc.28719. Epub 2014 Jan 25.
Rhabdoid tumors are highly aggressive tumors occurring in infants and very young children. Despite multimodal and intensive therapy prognosis remains poor. Molecular analyses have uncovered several deregulated pathways, among them the CDK4/6-Rb-, the WNT- and the Sonic hedgehog (SHH) pathways. The SHH pathway is activated in rhabdoid tumors by GLI1 overexpression. Here, we demonstrate that arsenic trioxide (ATO) inhibits tumor cell growth of malignant rhabdoid tumors in vitro and in a mouse xenograft model by suppressing Gli1. Our data uncover ATO as a promising therapeutic approach to improve prognosis for rhabdoid tumor patients.
横纹肌样瘤是发生于婴儿和非常年幼儿童的高度侵袭性肿瘤。尽管采用了多模式强化治疗，但其预后仍然很差。分子分析发现了几条失调的信号通路，其中包括细胞周期蛋白依赖性激酶4/6-视网膜母细胞瘤（CDK4/6-Rb）、WNT和音猬因子（SHH）信号通路。在横纹肌样瘤中，SHH信号通路通过GLI1的过表达而被激活。在此，我们证明三氧化二砷（ATO）通过抑制Gli1在体外和小鼠异种移植模型中抑制恶性横纹肌样瘤的肿瘤细胞生长。我们的数据揭示ATO是一种有望改善横纹肌样瘤患者预后的治疗方法。
