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.
KeywordsHepatic stellate cells Hsp90 inhibitor Proliferation Cell cycle
This study was supported by Grant 2007AA02Z301 of the National High Technology Research and Development Program of China (863 Program) and by Grant 07G603L056 of the New Drug Basic Research Program of the Shanghai Institute of Materia Medica, Chinese Academy of Sciences.
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