Everolimus is a potent inhibitor of activated hepatic stellate cell functions in vitro and in vivo, while demonstrating anti-angiogenic activities

Progression of liver fibrosis to hepatocellular carcinoma (HCC) is a very complex process which involves several pathological phenomenon including hepatic stellate cells activation, inflammation, fibrosis and angiogenesis. Therefore, inhibiting multiple pathological processes using a single drug can be an effective choice to curb the progression of HCC. In the present study, we used the mTOR inhibitor Everolimus to observe its effect on in vitro activation of hepatic stellate cells and angiogenesis. Our data demonstrated that Everolimus treatment blocked the functions of the immortalized human activated hepatic stellate cells LX-2 without affecting the viability and migration of primary human stellate cells. We also observed that treatment with Everolimus (20 nM) inhibited collagen production by activated stellate cells, as well as cell contraction. Everolimus treatment was also able to attenuate activation of primary stellate cells to its activated form. Angiogenesis studies showed that Everolimus blocked angiogenesis in rat aortic ring assay and inhibited the tube formation and migration of liver sinusoidal endothelial cells. Finally, Everolimus treatment reduced the load of tumoral myofibroblasts in a rat model of HCC. These data suggest that Everolimus targets multiple mechanisms, making it a potent blocker of the progression of HCC from liver fibrosis.
Source: Clinical Science - Category: Biomedical Science Authors: Source Type: research