Inhibition of hepatic stellate cell proliferation by heat shock protein 90 inhibitors in vitro.
Hepatic stellate cells (HSCs) play an important role in the development of hepatic fibrosis. Heat shock protein 90 (Hsp90) is essential for the maturation and activity of a varied group of proteins involved in signal transduction and cell cycle regulation. In this study, we found that two Hsp90 inhibitors, VER-49009 and its analog VER-49009M, inhibited the proliferation of hepatic stellate cell line CFSC cells, and both of them induced G2 phase arrest in CFSC cells. Akt expression was decreased by the treatment of Hsp90 inhibitors in CFSC cells. Based on these findings, we propose that the inhibition of Hsp90 might be a rational approach in the prevention of liver fibrosis.
Sun
Xu
X
Shanghai Institute of Materia Medica, Chinese Academy of Science, 201203, Shanghai, China.
Zhang
Xiao-Dong
XD
Cheng
Gang
G
Hu
You-Hong
YH
Wang
He-Yao
HY
D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D016195:G2 Phase / Q000187:drug effects; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D055166:Hepatic Stellate Cells / Q000166:cytology* / Q000473:pathology; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats
D018841:HSP90 Heat-Shock Proteins; D011720:Pyrazoles; C520150:VER-49009