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

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

doi:10.1042/bsr20200221

Abstract

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.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.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.

Highlights

Chordoma is the fourth most prevalent malignant cancer arising from notochordal remnant tissue and makes up approximately 1–4% of all bone malignancies [1]
These findings indicate that FTY720 effectively inhibits the growth of sacrum chordoma cells
Our findings indicate that FTY720 inhibited growth and epithelial–mesenchymal transition in sacral chordoma cells by deactivating the IL-6/STAT3 pathway

Summary

Introduction

Chordoma is the fourth most prevalent malignant cancer arising from notochordal remnant tissue and makes up approximately 1–4% of all bone malignancies [1]. Chordoma preferentially occurs in the axial skeleton and is most commonly found in the sacrum (50–60%) [2]. As chordoma is usually resistant to standard radiotherapy and chemotherapy, surgery is the main therapeutic approach [3]. Chordoma is often locally aggressive and associated with an elevated rate of recurrence, and recurrent chordoma can almost never be cured [4]. The cancer metastasizes in 5–40% of patients [5]. It is vital to find a novel and effective treatment strategy that can prolong the survival time of patients with chordoma [6]

Methods

Results

Conclusion