Fingolimod inhibits proliferation and epithelial–mesenchymal transition in sacral chordoma by inactivating IL-6/STAT3 signalling
Authors: Ying Sun
Shuai Han
Jiaqi Wang
Wenhao Hu
Xiaowen Du
Guanjun Tu
Journal: Bioscience reports (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: FTY720; IL-6/STAT3 signaling; epithelial-mesenchymal transition; proliferation; sacral chordoma.
Affiliations: 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., Department of Blood Transfusion, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110000, China., Department of Neurosurgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110000, China.

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 &lt; 0.01). FTY720 also inhibited the proliferation of tumour cells in a xenograft model using sacral chordoma cell lines (P &lt; 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. 

Retracted: No

PubPeer comments:
 There appears to be a repeated band in figure 2C, after flipping horizontally. *** ![file] *** ![file] *** ![file] , 
 https: doi.org 10.1042 BSR-20200221_EOC The Editorial Office has been made aware of potential issues surrounding the scientific validity of this paper, hence has issued an expression of concern to notify readers whilst the Editorial Office investigates. , 
 ** Retraction: Fingolimod inhibits proliferation and epithelial- mesenchymal transition in sacral chordoma by inactivating IL-6 STAT3 signaling** This Retraction follows an Expression of Concern relating to this article previously published by Portland Press. This article is being retracted from Bioscience Reports at the request of the authors following receipt of a notification from a reader, alerting the authors to duplications in the E-cadherin and Vimentin western blots in Figure 2C. The authors have been unable to replicate the results and wish to retract the article. The Editor-in-Chief and Editorial Board agree with the retraction. https: portlandpress.com bioscirep article 40 7 BSR-20200221_RET 225692 Retraction-Fingolimod-inhibits-proliferation-and ,