Wang Jiaqi, Hu Wenhao, Du Xiaowen, Sun Ying, Han Shuai, Tu Guanjun
Department of Orthopedics, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110000, China.
Department of Orthopedics, Chinese PLA General Hospital, Beijing 100853, P.R. China.
Biosci Rep. 2020 Feb 28;40(2). doi: 10.1042/BSR20200221.
To explore the sensitivity of the immunosuppressive agent fingolimod (FTY720) in chordoma and determine whether it can serve as an appropriate alternate treatment for unresectable tumours in patients after incomplete surgery.
Cell viability assays, colony formation assays and EdU assays were performed to evaluate the sensitivity of chordoma cell lines to FTY720. Transwell invasion assays, wound healing assays, flow cytometry, cell cycle analysis, immunofluorescence analysis, Western blotting analysis and enzyme-linked immunosorbent assays (ELISAs) were performed to evaluate cell invasion, epithelial-mesenchymal transition (EMT) and activation of related pathways after treatment with FTY720. The effect of FTY720 was also evaluated in vivo in a xenograft model.
We found that FTY720 inhibited the proliferation, invasion and metastasis of sacral chordoma cells (P < 0.01). FTY720 also inhibited the proliferation of tumour cells in a xenograft model using sacral chordoma cell lines (P < 0.01). The mechanism was related to the EMT and apoptosis of chordoma cells and inactivation of IL-6/STAT3 signalling in vitro and in vivo.
Our findings indicate that FTY720 may be an effective therapeutic agent against chordoma. These findings suggest that FTY720 is a novel agent that can treat locally advanced and metastatic chordoma.
探讨免疫抑制剂芬戈莫德（FTY720）对脊索瘤的敏感性，并确定其是否可作为不完全手术后不可切除肿瘤患者的合适替代治疗方法。
进行细胞活力测定、集落形成测定和EdU测定，以评估脊索瘤细胞系对FTY720的敏感性。进行Transwell侵袭测定、伤口愈合测定、流式细胞术、细胞周期分析、免疫荧光分析、蛋白质免疫印迹分析和酶联免疫吸附测定（ELISA），以评估用FTY720处理后细胞的侵袭、上皮-间质转化（EMT）及相关通路的激活情况。还在异种移植模型中对FTY720的体内效果进行了评估。
我们发现FTY720抑制骶骨脊索瘤细胞的增殖、侵袭和转移（P < 0.01）。FTY720在使用骶骨脊索瘤细胞系的异种移植模型中也抑制肿瘤细胞的增殖（P < 0.01）。其机制与体外和体内脊索瘤细胞的EMT和凋亡以及IL-6/STAT3信号通路的失活有关。
我们的研究结果表明，FTY720可能是一种有效的抗脊索瘤治疗药物。这些发现提示FTY720是一种可治疗局部晚期和转移性脊索瘤的新型药物。
