FNC efficiently inhibits mantle cell lymphoma growth

被引:9
|
作者
Zhang, Yan [1 ]
Zhang, Rong [2 ]
Ding, Xixi [3 ]
Peng, Bangan [3 ]
Wang, Ning [1 ]
Ma, Fang [1 ]
Peng, Youmei [1 ]
Wang, Qingduan [1 ]
Chang, Junbiao [4 ]
机构
[1] Zhengzhou Univ, Inst Med & Pharmaceut Sci, Zhengzhou, Henan, Peoples R China
[2] Sun Yat Sen Univ, Canc Ctr, Dept Endoscopy, State Key Lab Oncol South China,Collaborat Innova, Guangzhou, Guangdong, Peoples R China
[3] Zhengzhou Univ, Sch Pharmaceut Sci, Zhengzhou, Peoples R China
[4] Zhengzhou Univ, Coll Chem & Mol Engn, Zhengzhou, Peoples R China
来源
PLOS ONE | 2017年 / 12卷 / 03期
基金
中国国家自然科学基金;
关键词
NON-HODGKIN-LYMPHOMA; NUCLEOSIDE ANALOG; VORINOSTAT; RITUXIMAB;
D O I
10.1371/journal.pone.0174112
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
FNC, 2'-deoxy-2'-beta-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.
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页数:17
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