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 |
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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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