J Korean Ophthalmol Soc > Volume 55(7); 2014 > Article
Journal of the Korean Ophthalmological Society 2014;55(7):1077-1083.
DOI: https://doi.org/10.3341/jkos.2014.55.7.1077    Published online July 15, 2014.
Cytotoxicities and Anti-Fibrotic Effects of Pirfenidone and Mitomycin C on Human Fibroblasts.
Kyoung Soo Park, Sa Min Hong, Yoko Iizuka, Chan Yun Kim, Gong Je Seong
1Department of Ophthalmology, Siloam Eye Hospital, Seoul, Korea.
2The Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea. gjseong@yuhs.ac
인간 섬유아세포에 대한 마이토마이신 C와 피르페니돈의 독성과 항섬유화효과
박경수1⋅홍사민2⋅이주카요코2⋅김찬윤2⋅성공제2
Department of Ophthalmology, Siloam Eye Hospital1, Seoul, Korea The Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine2, Seoul, Korea
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.
Key Words: Anti-fibrotic effect;Cytotoxicity;Mitomycin C;Pirfenidone


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