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Zhang Y
; Zhang R
; Ding X
; Peng B
; Wang N
; Ma F
; Peng Y
; Wang Q
; Chang J
PLoS One
2017[]; 12
(3
): e0174112
PMID28333959
show ga
FNC, 2'-deoxy-2'-?-fluoro-4'-azidocytidine, is a novel cytidine analogue, that
has shown strong antiproliferative activity in human lymphoma, lung
adenocarcinoma and acute myeloid leukemia. In this study, we investigated the
effects of FNC on mantle cell lymphoma (MCL) and the underlying mechanisms. In in
vitro experiments, cell viability was detected by the CCK8 assay, and cell cycle
progression and apoptosis were assessed by flow cytometry, and the expression of
relative apoptosis proteins were detected by Western Blot. The in vivo antitumor
effect of FNC was investigated in a SCID xenograft model. Finally, the mechanisms
of action of FNC were assessed using a whole human genome expression profile
chip. The data showed that FNC inhibited cell growth in a dose- and
time-dependent manner, and FNC could induce apoptosis by the death recepter
pathways in JeKo-1 cells and arrest the cell cycle in the G1/S or G2/M phase.
Notably, FNC showed in vivo efficacy in mice bearing JeKo-1 xenograft tumors.
Gene expression profile analysis revealed that the differentially expressed genes
were mainly focused on the immune system process, cellular process and death.
These findings implied that FNC may be a valuable therapeutic in mantle cell
lymphoma and provided an experimental basis for the early clinical application of
FNC.
|Animals
[MESH]
|Antineoplastic Agents/*therapeutic use
[MESH]
|Apoptosis/drug effects
[MESH]
|Blotting, Western
[MESH]
|Cell Cycle/drug effects
[MESH]
|Cell Line, Tumor
[MESH]
|Cell Proliferation/drug effects
[MESH]
|Cell Survival/drug effects
[MESH]
|Deoxycytidine/*analogs & derivatives/therapeutic use
[MESH]