A study of the combination of triamcinolone and 5-fluorouracil in modulating keloid fibroblasts in vitro
A study of the combination of triamcinolone and 5-fluorouracil in modulating keloid fibroblasts in vitro
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DOI：
10.1016/j.bjps.2013.06.004
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发表时间：
2013-09-01
影响因子：
2.7
通讯作者：
Burd, Andrew
中科院分区：
文献类型：
--
作者：
Huang, Lin;Cai, Yi J.;Burd, Andrew
背景资料：初步临床试验表明，当类固醇和5-氟尿嘧啶一起注射用于瘢痕疙瘩的病灶内治疗时，具有上级效果。此外，已经提出低剂量5-氟尿嘧啶可能比常规高剂量具有优势。我们探索了曲安西龙和5-氟尿嘧啶联合治疗中潜在协同作用的分子基础。单独或与低剂量5-氟尿嘧啶组合的曲安西龙对细胞增殖、细胞周期进展、凋亡和p53、p21、I型胶原（Col-1）、血管内皮生长因子（VEGF）、转化生长因子β 1 MTT法检测原代培养瘢痕疙瘩成纤维细胞TGF-β 1和MMP-2的表达（3-（4，5-二甲基噻唑-2-基）-2，5-二苯基四唑溴化物）、流式细胞术和蛋白质印迹分析。曲安西龙抑制细胞增殖，诱导G1期细胞阻滞，但不诱导凋亡。相比之下，5-氟尿嘧啶诱导G2期细胞周期阻滞和细胞凋亡，这可能与p53激活和p21上调有关。Col-1，VEGF，TGF-β 1和MMP-2的表达的调节曲安西龙和5-氟尿嘧啶单独或其组合在各个细胞系之间变化;趋势是促进Col-1和TGF-β 1的减少，但MMP-2的表达上调。5-氟尿嘧啶在联合治疗中发挥了主导作用，导致更显著的细胞增殖抑制、凋亡、Col-1抑制和MMP-2诱导（p < 0.05）。结论：我们的数据提供了基于分子的证据，证明了在类固醇注射中加入5-氟尿嘧啶对改善瘢痕消退和减少瘢痕疙瘩复发的临床益处。我们预计，当使用较低治疗剂量的单独药物时，联合治疗的不良副作用较少。(C)2013年英国整形、重建和美容外科医生协会。由爱思唯尔有限公司出版。保留所有权利。
Background: Preliminary clinical trials suggest a superior effect when steroids and 5-fluorouracil are injected together for the intralesional therapy of keloids. In addition, it has been proposed that low-dose 5-fluorouracil may have advantages over conventional high dosages. We explored the molecular basis for the potential synergy involved in the combined treatment with triamcinolone and 5-fluorouracil.Methods: The effects of triamcinolone alone or in combination with low-dose 5-fluorouracil on cell proliferation, cell-cycle progression, apoptosis and regulation of p53, p21, type I collagen (Col-1), vascular endothelial growth factor (VEGF), transforming growth factor-beta1 (TGF-beta1) and matrix metalloproteinase-2 (MMP-2) production in primary cultured keloid fibroblasts were examined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), flow cytometric and Western blotting assays.Results: Triamcinolone suppressed cell proliferation and induced G1 cell-cycle arrest but not apoptosis. By contrast, 5-fluorouracil induced G2 cell-cycle arrest and apoptosis that may be associated with p53 activation and p21 up-regulation. The modulation of Col-1, VEGF, TGF-beta1 and MMP-2 expression by triamcinolone and 5-fluorouracil alone or their combination varied between individual cell lines; the trend is to promote a reduction in Col-1 and TGF-beta1 but up-regulation of MMP-2 expression. 5-Fluorouracil played a predominant role in the combined treatment leading to more significant cell proliferation inhibition, apoptosis, Col-1 suppression and MMP-2 induction (p < 0.05).Conclusions: Our data provide the molecular-based evidence for the observed clinical benefits of adding 5-fluorouracil to a steroid injection for improved scar regression and reduced recurrence of keloids. We expect fewer undesirable side effects in the combined treatment when the lower therapeutic dose of the individual drugs is to be used. (C) 2013 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.