Anti angiogenic effects in mice with hepatocarcinoma and liver fibrosis

PICCIONI F; LLOYD R; RIZZO M; FIORE E; BAYO J; PEIXOTO E; MALVICINI M; GARCIA MG; ALANIZ L; MAZZOLINI G

Simposio; I Simposio argentino de Glicobiologia; 2014

Cirrhosis is characterized by an excessive accumulation of extracellular matrix components including hyaluronic acid (HA), and is a pre-neoplasic disease which results in development of hepatocellular carcinoma (HCC). HCC is one of the most vascularized solid tumors. 4 -methylumbelliferone (4MU) a bioavailable oral agent, is a specific inhibitor of the synthesis of HA which exerts an antitumor effect in our model of orthotopic HCC with underlying fibrosis established in mice. It has been observed that HA has an effect on angiogenesis. To determine if inhibition of HA synthesis affects angiogenesis in our experimental model. We inoculated Hepa129 tumor cells in the liver of C3H/HeJ male mice with advanced liver fibrosis. Fibrosis was induced by i.p. inyections of thyoacetamide for 42 days. Then, mice were orally treated with 4MU for 17 days. We evaluated effects on angiogenesis in vivo by detecting VEGF in serum and liver tissue of mice treated or not with 4MU, by ELISA. We also analyzed VEGF expression in liver tissue and tumor by qPCR. 4MU treatment significantly reduced systemic and local VEGF. Expression of VEGF mRNA was significantly reduced in mice treated with 4MU only in non tumor liver parenchyma, in comparison to untreated mice. Our results suggest that 4MU has antiangiogenic effects in the studied model.