Paclitaxel ameliorates fibrosis in hepatic stellate cells via inhibition of TGF-beta/Smad activity.

AIM: To investigated if paclitaxel can attenuate hepatic fibrosis in rat hepatic stellate cells (RHSCs).

METHODS

RHSCs were cultured in vitro and randomly assigned to four groups: normal control group (treated only with Dulbecco's Modified Eagle's Medium), Taxol group (200 nmol/L paclitaxel was added to the cell culture), transforming growth factor (TGF)-beta group (5 ng/mL recombinant human TGF-beta1 was added to the cell culture), and TGF-beta + Taxol group. TGF-beta signaling cascade and status of various extracellular matrix proteins were evaluated by real time reverse transcriptase polymerase chain reaction and Western blotting.

RESULTS

The paclitaxel treatment markedly suppressed Smad2/3 phosphorylation. This was associated with attenuated expression of collagen I and III and fibronectin in RHSCs.

CONCLUSION

These data indicate that 200 nmol/L paclitaxel ameliorates hepatic fibrosis via modulating TGF-beta signaling, and that paclitaxel may have some therapeutic value in humans with hepatic fibrosis.