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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Am+J+Transl+Res
2016 ; 8
(11
): 4548-4563
Nephropedia Template TP
gab.com Text
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English Wikipedia
A novel sphingosine kinase 1 inhibitor (SKI-5C) induces cell death of Wilms
tumor cells in vitro and in vivo
#MMPMID27904661
Li ZH
; Tao YF
; Xu LX
; Zhao H
; Li XL
; Fang F
; Wu Y
; Lu J
; Li YH
; Du WW
; Ren JL
; Li YP
; Xu YY
; Feng X
; Wang J
; He WQ
; Pan J
Am J Transl Res
2016[]; 8
(11
): 4548-4563
PMID27904661
show ga
Sphingosine kinase 1 (SphK1) is over-expressed in many cancers and therefore
serves as a biomarker for cancer prognosis. SKI-5C is a new SphK1 inhibitor, and
until now its molecular function in Wilms' tumor cells remained unknown. Here,
using CCK-8 and nude mice experiments we assessed cell growth in Wilms' tumor
cell lines (SK-NEP-1 and G401) in vitro and in vivo. We demonstrated that SphK1
is highly expressed in SK-NEP-1 and G401 cells, and through annexin V/propidium
iodide staining and flow cytometry analysis, we detected cell apoptosis.
Treatment with SKI-5C inhibited proliferation and induced apoptosis of SK-NEP-1
and G401 cells in a dose-dependent manner. Moreover, SKI-5C treatment inhibited
the growth of SK-NEP-1 xenograft tumors in nude mice, with few side effects. Our
microarray analysis revealed that SKI-5C-treated SK-NEP-1 cells mostly
downregulated PRKACA and significantly inhibited phosphorylation of ERK1/2 and
NF-?B p65. These results imply that SKI-5C induces apoptosis of SK-NEP-1 cells
through the PRKACA/MAPK/NF-?B pathway. While, further research is required to
determine the underlying details, these results provide new clues for the
molecular mechanism of cell death induced by SKI-5C and suggest that SKI-5C may
act as new candidate drug for Wilms' tumor.