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Cytotoxicities and Anti-Fibrotic Effects of Pirfenidone and Mitomycin C on Human Fibroblasts

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¹Ú°æ¼ö(Park Kyoung-Soo) - ½Ç·Î¾Ï ¾È°úº´¿ø
È«»ç¹Î(Hong Sa-Min) - ¿¬¼¼´ëÇб³ Àǰú´ëÇÐ ¾È°úÇб³½Ç
ÀÌÁÖÄ«¿äÄÚ(Iizuka Yoko) - ¿¬¼¼´ëÇб³ Àǰú´ëÇÐ ¾È°úÇб³½Ç
±èÂùÀ±(Kim Chan-Yun) - ¿¬¼¼´ëÇб³ Àǰú´ëÇÐ ¾È°úÇб³½Ç
¼º°øÁö(Seong Gong-Je) - ¿¬¼¼´ëÇб³ Àǰú´ëÇÐ ¾È°úÇб³½Ç

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)-¥â1, different concentrations of mitomycin C, and pirfenidone solutions in order to evaluate cytotoxicity. Expressions of fibronectin, collagen type 1, ¥á smooth muscle, and ¥â-actin were evaluated by real-time reverse transcription-polymerase chain reaction (RT-PCR) and western blot in mitomycin C solutions at concentrations of 4 ¥ìg/mL and 20 ¥ìg/mL, and in pirfenidone solutions at 250 ¥ìg/mL and 500 ¥ìg/mL.

Results: In comparison to cell cultures exposed to TGF-¥â1 solutions, cytotoxicities were increased in solutions of mitomycin C at 4 ¥ìg/mL, 20 ¥ìg/mL, 40 ¥ìg/mL and pirfenidone at 500 ¥ìg/mL, 750 ¥ìg/mL, 1,000 ¥ìg/mL (p < 0.05, Mann Whitney U-test). The results of real-time RT-PCR show that expressions of fibronectin, collagen type 1, and ¥á smooth muscle were significantly more decreased in all concentrations of mitomycin C and pirfenidone compared to those in TGF-¥â1 solution. In western blot analysis, expressions of fibronectin and ¥á smooth muscle were decreased in all concentrations of mitomycin C and pirfenidone compared to TGF-¥â1 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.

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Anti-fibrotic effect, Cytotoxicity, Mitomycin C, Pirfenidone
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