The Inhibitory Effects of the Antifibrotic Drug Halofuginone скачать в хорошем качестве

The Inhibitory Effects of the Antifibrotic Drug Halofuginone

The Inhibitory Effects of the Antifibrotic Drug Halofuginone on Uterine Leiomyoma Smooth Muscle Cells Friday, April 6, 2012 • 9:50-10:05 AM Authors: Faezeh Koohestani*, Wenan Qiang, Takeshi Kurita, Maureen Getty, Jacob Schanks, Amy MacNeill, and Romana Nowak Uterine leiomyomas are the most prevalent benign tumors of the reproductive tract in women. Available treatments for leiomyomas are limited to surgical procedures or hormonal therapy, which are costly and have significant side effects. In an effort to develop alternative therapeutic strategies, we tested the drug halofuginone (HF) in primary leiomyoma smooth muscle cells (LSMCs) in vitro and in vivo. Our results show that treatment of LSMCs with 50nM HF in vitro caused a significant decrease in cell proliferation and expression of collagens, which are hallmarks of these tumors. These effects were also found to be mediated through the MAPK and SRC pathways. We next tested the inhibitory effects of HF in an in vivo leiomyoma-xenografted mouse model. Treatment of mice with 0.25 mg/kg/day HF for four weeks significantly reduced the size of tumors by 50% with no effect on body weight or overall health of the animals. HF also caused a decrease in cell proliferation and increased in apoptosis. Our findings demonstrate that the antifibrotic drug HF inhibits the growth of leiomyomas through its effects on major cell signaling pathways, and may lead to the development of HF as an efficient therapeutic strategy for treatment of these common tumors.