Brack Eva, Bender Sabine, Wachtel Marco, Pruschy Martin, Schäfer Beat W
Department of Oncology, Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland.
Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland.
Front Oncol. 2021 Jun 15;11:664462. doi: 10.3389/fonc.2021.664462. eCollection 2021.
Fusion-positive rhabdomyosarcoma (FP-RMS) is a highly aggressive childhood malignancy which is mainly treated by conventional chemotherapy, surgery and radiation therapy. Since radiotherapy is associated with a high burden of late side effects in pediatric patients, addition of radiosensitizers would be beneficial. Here, we thought to assess the role of fenretinide, a potential agent for FP-RMS treatment, as radiosensitizer. Survival of human FP-RMS cells was assessed after combination therapy with fenretinide and ionizing radiation (IR) by cell viability and clonogenicity assays. Indeed, this was found to significantly reduce cell viability compared to single treatments. Mechanistically, this was accompanied by enhanced production of reactive oxygen species, initiation of cell cycle arrest and induction of apoptosis. Interestingly, the combination treatment also triggered a new form of dynamin-dependent macropinocytosis, which was previously described in fenretinide-only treated cells. Our data suggest that fenretinide acts in combination with IR to induce cell death in FP-RMS cells and therefore might represent a novel radiosensitizer for the treatment of this disease.
融合阳性横纹肌肉瘤（FP-RMS）是一种侵袭性很强的儿童恶性肿瘤，主要通过传统化疗、手术和放射治疗。由于放射治疗会给儿科患者带来较高的晚期副作用负担，添加放射增敏剂会有益处。在此，我们想评估视黄酸乙酯（一种用于FP-RMS治疗的潜在药物）作为放射增敏剂的作用。通过细胞活力和克隆形成试验评估视黄酸乙酯与电离辐射（IR）联合治疗后人FP-RMS细胞的存活率。事实上，与单一治疗相比，发现这种联合治疗能显著降低细胞活力。从机制上讲，这伴随着活性氧生成增加、细胞周期停滞的启动和细胞凋亡的诱导。有趣的是，联合治疗还引发了一种新的依赖发动蛋白的巨胞饮作用形式，这在仅用视黄酸乙酯治疗的细胞中曾有描述。我们的数据表明，视黄酸乙酯与IR联合作用可诱导FP-RMS细胞死亡，因此可能代表一种治疗该疾病的新型放射增敏剂。
