Fingolimod inhibits proliferation and epithelial-mesenchymal transition in sacral chordoma by inactivating IL-6/STAT3 signalling

芬戈莫德通过抑制 IL-6/STAT3 信号传导来抑制骶骨脊索瘤的增殖和上皮-间质转化

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作者:Jiaqi Wang, Wenhao Hu, Xiaowen Du, Ying Sun, Shuai Han, Guanjun Tu

Conclusions

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.

Methods

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.

Purpose

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.

Results

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. Conclusions: 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.

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