当前位置： SCI文献检索 > BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS期刊下所有文献 > Targeting sphingosine kinase 2 by ABC294640 inhibits human skin squamous cell carcinoma cell growth.

Targeting sphingosine kinase 2 by ABC294640 inhibits human skin squamous cell carcinoma cell growth.

Abstract：

:The activity of ABC294640, a small-molecular sphingosine kinase 2 (SphK2) inhibitor, in human skin squamous cell carcinoma (SCC) cells was tested in this study. SphK2 mRNA and protein are expressed in established (A431 cheilocarcinoma cell line) and primary human skin SCC cells. ABC294640 dose-dependently inhibited survival, cell cycle progression and proliferation of skin SCC cells. Furthermore, ABC294640 induced caspase-3/-9 and apoptosis activation in skin SCC cells. The SphK2 inhibitor was however non-cytotoxic to SphK2-null skin melanocytes, keratinocytes and fibroblasts. ABC294640 induced ceramide accumulation, sphingosine-1-phosphate (S1P) reduction, Akt-S6K1 inhibition and JNK activation in skin SCC cells. Conversely, its cytotoxicity against SCC cells was largely attenuated by co-treatment of S1P, the Akt activator SC79, and the JNK inhibitor SP600125. In vivo, ABC294640 oral administration inhibited A431 xenograft tumor growth in nude mice. Akt-S6K1 inhibition and JNK activation were observed in ABC294640-treated tumors. Collectively, ABC294640 efficiently inhibits human skin SCC cell growth in vitro and in vivo.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Zhou J,Chen J,Yu H

doi

10.1016/j.bbrc.2018.02.075

subject

Has Abstract

pub_date

2018-03-04 00:00:00

pages

535-542

issue

2

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(18)30298-5

journal_volume

497

pub_type

杂志文章

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