Cytotoxicities and Anti-Fibrotic Effects of Pirfenidone and Mitomycin C on Human Fibroblasts.
10.3341/jkos.2014.55.7.1077
- Author:
Kyoung Soo PARK
1
;
Sa Min HONG
;
Yoko IIZUKA
;
Chan Yun KIM
;
Gong Je SEONG
Author Information
1. Department of Ophthalmology, Siloam Eye Hospital, Seoul, Korea.
- Publication Type:Original Article
- Keywords:
Anti-fibrotic effect;
Cytotoxicity;
Mitomycin C;
Pirfenidone
- MeSH:
Actins;
Blotting, Western;
Cell Culture Techniques;
Collagen;
Fibroblasts*;
Fibronectins;
Humans;
Mitomycin*;
Muscle, Smooth;
Transforming Growth Factor beta1;
Transforming Growth Factors
- From:Journal of the Korean Ophthalmological Society
2014;55(7):1077-1083
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
PURPOSE: The cytotoxicities and anti-fibrotic effects of mitomycin C and pirfenidone on human dermal fibroblast were evaluated. METHODS: Initially, 24-hour cell cultures were exposed to transforming growth factor (TGF)-beta1, different concentrations of mitomycin C, and pirfenidone solutions in order to evaluate cytotoxicity. Expressions of fibronectin, collagen type 1, alpha smooth muscle, and beta-actin were evaluated by real-time reverse transcription-polymerase chain reaction (RT-PCR) and western blot in mitomycin C solutions at concentrations of 4 microg/mL and 20 microg/mL, and in pirfenidone solutions at 250 microg/mL and 500 microg/mL. RESULTS: In comparison to cell cultures exposed to TGF-beta1 solutions, cytotoxicities were increased in solutions of mitomycin C at 4 microg/mL, 20 microg/mL, 40 microg/mL and pirfenidone at 500 microg/mL, 750 microg/mL, 1,000 microg/mL (p < 0.05, Mann Whitney U-test). The results of real-time RT-PCR show that expressions of fibronectin, collagen type 1, and alpha smooth muscle were significantly more decreased in all concentrations of mitomycin C and pirfenidone compared to those in TGF-beta1 solution. In western blot analysis, expressions of fibronectin and alpha smooth muscle were decreased in all concentrations of mitomycin C and pirfenidone compared to TGF-beta1 solution. CONCLUSIONS: Both drugs have cytotoxicities and anti-fibrotic effects, but pirfenidone was found to have less cytotoxicity and mitomycin C was found to have more anti-fibrotic effects when compared to each other.
