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.FNC（2'-deoxy-2'-β-fluoro-4'-azidocytidine）是一种新型胞苷类似物，已在人淋巴瘤、肺腺癌及急性髓系白血病中展现出强劲的抗增殖活性。本研究旨在探讨FNC对套细胞淋巴瘤（mantle cell lymphoma, MCL）的作用及其潜在分子机制。体外实验中，采用CCK8法检测细胞活力，通过流式细胞术分析细胞周期进程与细胞凋亡情况，利用蛋白质印迹法（Western Blot）检测相关凋亡蛋白的表达水平；体内实验则通过重症联合免疫缺陷（SCID）异种移植模型评估FNC的抗肿瘤效应。最后，借助全人类基因组表达谱芯片解析FNC的作用机制。实验数据表明，FNC可通过剂量与时间依赖性方式抑制细胞生长，且在JeKo-1细胞中能够通过死亡受体通路诱导细胞凋亡，并将细胞周期阻滞于G1/S期或G2/M期。值得注意的是，FNC在携带JeKo-1异种移植瘤的小鼠中展现出体内抗肿瘤活性。基因表达谱分析显示，差异表达基因主要富集于免疫过程、细胞过程及细胞死亡相关通路。上述研究结果提示，FNC或可成为套细胞淋巴瘤的潜在治疗药物，为其早期临床应用提供了实验依据。