FNC efficiently inhibits mantle cell lymphoma growth.
FNC, 2'-deoxy-2'-β-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.
Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Henan, China.
Yan
Y
Zhang
Department of Endoscopy, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
Rong
R
Zhang
School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.
Xixi
X
Ding
School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.
Bangan
B
Peng
Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Henan, China.
Ning
N
Wang
Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Henan, China.
Fang
F
Ma
Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Henan, China.
Youmei
Y
Peng
Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Henan, China.
Qingduan
Q
Wang
College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou, China.
Junbiao
J
Chang
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy*; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D016133:Polymerase Chain Reaction
C000596970:2'-deoxy-2'-fluoro-4'-azidocytidine; D000970:Antineoplastic Agents; D003841:Deoxycytidine