Low-dose 5-fluorouracil induces cell cycle G2 arrest and apoptosis in keloid fibroblasts
Low-dose 5-fluorouracil induces cell cycle G2 arrest and apoptosis in keloid fibroblasts
复制标题
DOI：
10.1111/j.1365-2133.2010.09939.x
复制
发表时间：
2010-12-01
影响因子：
10.3
通讯作者：
Burd, A.
中科院分区：
文献类型：
--
作者：
Huang, L.;Wong, Y. P.;Burd, A.
背景低剂量5-氟尿嘧啶（5-FU）病灶内注射治疗瘢痕疙瘩是目前治疗瘢痕疙瘩的一种实验方法，在改善瘢痕外观和预防瘢痕疙瘩复发方面显示出良好的疗效。结果5-FU对瘢痕疙瘩成纤维细胞的增殖有明显的抑制作用，其剂量范围为10 mg/mL ~（-1），对细胞活力、增殖能力、凋亡、细胞周期及相关蛋白的表达有明显的抑制作用。DNA合成在72 h时被5-FU完全抑制，在浓度>= 1 mg/mL（-1）时观察到显著的细胞凋亡，持续时间超过72 h。5-FU可明显延缓细胞周期进程，使细胞阻滞于G2/M期。结论低剂量5-FU（1 mg·mL ~（-1））可明显抑制瘢痕疙瘩成纤维细胞的增殖，使细胞周期阻滞于G2/M期，并诱导细胞凋亡，但不能使瘢痕疙瘩成纤维细胞立即死亡。组织坏死的缺乏是一个特别的好处，因为进一步的疤痕可能被防止。这些结果支持使用低剂量5-FU作为治疗瘢痕疙瘩的潜在方式。
Background Intralesional injection of low-dose 5-fluorouracil (5-FU) has recently been used as an experimental modality for treating keloid scarring and has shown promising efficacy in improving scar appearance and preventing recurrence of the keloid.Objectives We sought to explore the cellular-and molecular-based evidence for the observed clinical benefits.Methods Primary cell lines of keloid fibroblasts were treated with 5-FU at a range of lower doses (similar to 10 mg mL(-1)) in monolayer culture and subjected to examination for cell viability, proliferative potential, apoptosis, cell cycle and associated proteins involved in cell cycle control.Results 5-FU significantly inhibited cell proliferation of keloid fibroblasts in the full dose range used in this study. The DNA synthesis was completely inhibited by 5-FU at 72 h, and significant cell apoptosis was observed at concentrations >= 1 mg mL(-1) for a period over 72 h. 5-FU caused a significant delay in cell cycle progression and the G2/M phase arrest. 5-FU induced p53 and p21 accumulation together with a decrease in cyclin B1 and Bcl-2 levels in treated keloid fibroblasts.Conclusions Our data indicate that low-dose 5-FU (as low as 1 mg mL(-1)) induces significant inhibition of proliferation, G2/M cell cycle arrest and apoptosis but not immediate cell death of keloid fibroblasts. The lack of tissue necrosis is a particular benefit as further scarring is likely to be prevented. These results support the use of low-dose 5-FU as a potential modality for treating keloid scars.