Oncotarget

Research Papers:

Sphingosine kinase 1 is a potential therapeutic target for nasopharyngeal carcinoma

Wenhua Li, Jian Li, Yunchao Wang, Keqian Zhang, Ni Li, Zhiqiang Tian, Bing Ni, Huaizhi Wang and Zhihua Ruan _

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Oncotarget. 2016; 7:80586-80598. https://doi.org/10.18632/oncotarget.13014

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Abstract

Wenhua Li1,*, Jian Li2,*, Yunchao Wang2, Keqian Zhang1, Ni Li1, Zhiqiang Tian3, Bing Ni4,3, Huaizhi Wang2, Zhihua Ruan1

1Department of Oncology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China

2Institute of Hepatopancreatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China Institute of Hepatopancreatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, PR China

3Institute of Immunology, PLA, Third Military Medical University, Chongqing 400038, PR China

4Department of Pathophysiology and High Altitude Pathology, Third Military Medical University, Chongqing 400038, PR China

*These authors contributed equally to this work

Correspondence to:

Bing Ni, email: [email protected]

Huaizhi Wang, email: [email protected]

Zhihua Ruan, email: [email protected]

Keywords: nasopharyngeal carcinoma, sphingosine kinase 1, therapeutic target, FTY720

Received: September 09, 2016     Accepted: October 25, 2016     Published: November 02, 2016

ABSTRACT

Sphingosine kinase 1 (SPHK1) has been shown to be involved in the progression of various types of human cancers. We previously demonstrated that SPHK1 is overexpressed and associated with clinical stage, locoregional recurrence, distant metastasis and poor prognosis in nasopharyngeal carcinoma (NPC). However, the biological roles involving SPHK1 and its potential usefulness as a therapeutic target in NPC remain unknown. In this study, Blocking SPHK1 using siRNA or FTY720 (a SPHK1 inhibitor) significantly reduced proliferation and migration and increased cell cycle arrest and apoptosis in NPC cells. FTY720 also decreased SPHK1 activity, and overexpressing SPHK1 abrogated the FTY720-induced effects on cell viability. In addition, FTY720 sensitized NPC cells to radiotherapy by inhibiting SPHK1 activity in vitro and in vivo. Furthermore, high SPHK1 expression was associated with increased Ki-67 and p-Akt and decreased caspase-3 expression in human NPC specimens. These data suggest that SPHK1 might be a potential therapeutic target for NPC.


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