Effect of pirfenidone and its combination with 5-fluorouracil on keloid fibroblast proliferation and collagen deposition: in vitro study

Abstract

Background: Keloid is a fibroproliferative disease in which its etiology remains unknown. Various therapy modalities have been improved, but none of them gives a satisfying outcome. Pirfenidone (PFD) is a commonly used drug in pulmonary fibrotic diseases, which has an anti-fibrotic effect. 5-fluorouracil (5-FU) is one of the keloid therapy choices that has long been used. This study aimed to investigate PFD's effect and its combination with 5-FU on fibroblast proliferation and collagen deposition.Methods: This experimental study using post only control group design was conducted by comparing PFD in various doses (0.5, 1.0, 1.5, 2.0, 3.0 mg/ml) and its combination with 5-FU on keloid fibroblast proliferation and collagen deposition. We used MTT (3-[4,5-dimethylthiazol-2-yl}-2,5diphenyl tetrazolium bromide) and Sirius Red assays to measure the fibroblast proliferation and collagen deposition, respectively. The statistical analysis used one-way ANOVA with p-value p<0.05 was considered significant.Results: The combination of PFD 3.0 mg/ml + 5-FU 1.0 mg/ml had more significant effect on inhibiting fibroblast proliferation as well as decreasing collagen deposition compared to 5-FU only (p<0.043). PFD 1.0 mg/ml + 5-FU 1 mg/ml as well as PFD 1.5 mg/ml+ 5-FU 1 mg/ml are more effective in inhibiting fibroblast proliferation and lowering collagen deposition than PFD only with p values of <0.001 and <0.000, respectively.Conclusion: In general, PFD, as well as 5-FU, are effective in inhibiting fibroblast proliferation and decreasing collagen deposition in keloid. However, the combination of both has a better effect compared to PFD or 5-FU monotherapy.