Objective To study the anti-proliferative effects of okam J201 on human embryonic pulmonary fibroblast (HPF) and its underlying mechanisms.Methods The effect of J201 on the proliferation of HPF was evaluated by MTT assay. And the result was compared with the control group. The effect of J201 on DNA and protein synthesis of HPF was studied by flow cytometry (FCM). Furthermore, the inhibitory effect of J201 on PDGF-mediated HPF proliferation was observed by MTT. Effect of J201 on the reduced apoptosis of HPF by TGF- 3 in serum-free media was also observed by FCM.Results J201 inhibited the proliferation of HPF in a dose-dependent manner at concentrations from1 g/ml to 100 g/ml, with its maximal inhibitory rate(56.02%, P<0.01) at 100 g/ml. HPF was blocked at G0/G1 phase of cell cycle and its protein synthesis was also inhibited by J201. Moreover, J201 led to a dose-dependent inhibition of PDGF-mediated HPF proliferation. The reduced apoptosis of HPF in serum-free media in the presence of TGF- was restored by J201 in a dose-dependent manner.Conclusion J201 exerted its antifibrotic activity by inhibiting HPF at G0/G1 stage of cell cycle and the synthesis of proteins. The interaction of J201 with PDGF and TGF- may be involved in its anti-proliferative mechanisms. These data suggest that J201 has properties which may be beneficial in the treatment of pulmonary fibrosis. |