L Huang1, Y P Wong, Y J Cai, I Lung, C S Leung, A Burd. 1. Division of Plastic, Reconstructive and Aesthetic Surgery, Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.
Abstract
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 (∼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.
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 (∼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.
Authors: Hongyi Wang; Liangliang Quan; Jiulong Liang; Jie Shi; Tao Qiu; Ye Zhang; Yang Wang; Qiang Hui; Yu Zhang; Kai Tao Journal: Exp Ther Med Date: 2017-10-03 Impact factor: 2.447
Authors: Sebastian P Nischwitz; Katharina Rauch; Hanna Luze; Elisabeth Hofmann; Alexander Draschl; Petra Kotzbeck; Lars-Peter Kamolz Journal: Wound Repair Regen Date: 2020-06-15 Impact factor: 3.617