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


CONCLUSIONS
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.
Zhou
Jun
J
Department of Hepatobiliary Surgery, Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China.
Zhong
De-Wu
DW
Wang
Qun-Wei
QW
Miao
Xiong-Ying
XY
Xu
Xun-Di
XD
D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D017931:DNA Primers / Q000235:genetics; D055166:Hepatic Stellate Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D051785:Smad Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000494:pharmacology; D050257:Tubulin Modulators / Q000494:pharmacology
D017931:DNA Primers; D012333:RNA, Messenger; D011994:Recombinant Proteins; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; D050257:Tubulin Modulators; D017239:Paclitaxel