Comparison of in-vitro anti-fibrotic effects of pirfenidone and nintedanib / 中国药理学通报

ABSTRACT

Aim To compare the mechanism of action of currently marketed pulmonary fibrosis drugs at the cellular level by evaluating the inhibitory effects of pirfenidone and nintedanib on the proliferation, migration and activation of human embryonic lung fibroblast HFL1. Methods The inhibitory effects of pirfenidone and nintedanib on TGF-β1/PDGF-induced HFL1 proliferation, migration and activation were evaluation of by MTT, scratch test,Q-PCR and Western blot. Results MTT, scratch test results showed that both pirfenidone and nintedanib could inhibit TGF-β1-induced fibroblast proliferation and migration, in which nintedanib had a higher titer than pirfenidone. In anti-activation experiments, both pirfenidone and nintedanib inhibited the expression of fibroblast activation markers mRNA and protein, and both inhibited the phosphorylation of Smad3 and inhibited the activation of TGF-β/ Smad3 signaling pathway. Nintedanib had a stronger inhibitory effect on TGF-β/Smad3 signaling pathway, which exerted 51 % inhibitory rate on Smad3 phosphorylation compared with 13% inhibitory rate of pirfenidone. Conclusions Both pirfenidone and nintedanib can inhibit the proliferation, migration and activation of myofibroblasts, where nintedanib has a higher inhibitory potency than pirfenidone does, and the inhibition of TGF-β/Smad3 signaling pathway is stronger.