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Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2015

Open Access 01-12-2015 | Research

Targeting sphingosine kinase 2 (SphK2) by ABC294640 inhibits colorectal cancer cell growth in vitro and in vivo

Authors: Cai Xun, Min-Bin Chen, Li Qi, Zhang Tie-Ning, Xue Peng, Li Ning, Chen Zhi-Xiao, Wang Li-Wei

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2015

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Abstract

Background

Colorectal cancer (CRC) is a major health problem in China and around the world. It is one of the leading causes of cancer-related deaths. Research groups are thus searching for novel and more efficient anti-CRC agents.

Results

Here we demonstrated that ABC294640, a novel SphK2 inhibitor, induced growth inhibition and apoptosis in transformed and primary CRC cells. The SphK activity was remarkably inhibited by ABC294640, accompanied by sphingosine-1-phosphate (S1P) depletion and ceramide incensement in CRC cells. Exogenously-added S1P inhibited ABC294640-induced HT-29 cell lethality. While C6 ceramide and SphK1 inhibitor SKI-II facilitated ABC294640-induced cytotoxicity against HT-29 cells. ABC294640 inhibited AKT-S6K1, but activated JNK signaling in transformed and primary CRC cells. JNK inhibitors (SP600125 and JNKi-II) alleviated ABC294640-induced CRC cell apoptosis. Moreover, a low concentration of ABC294640 sensitized the activity of 5-FU and cisplatin in vitro. In vivo, ABC294640 oral administration dramatically inhibited HT-29 xenografts growth in nude mice.

Conclusions

Targeting of SphK2 by ABC294640 potently inhibits CRC cell growth both in vitro and in vivo, ABC294640 could be developed as a novel therapeutic for the treatment of CRC.
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Metadata
Title
Targeting sphingosine kinase 2 (SphK2) by ABC294640 inhibits colorectal cancer cell growth in vitro and in vivo
Authors
Cai Xun
Min-Bin Chen
Li Qi
Zhang Tie-Ning
Xue Peng
Li Ning
Chen Zhi-Xiao
Wang Li-Wei
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2015
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-015-0205-y

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