Abstract
Abstract Sorafenib is a multikinase inhibitor with activity against Raf kinase and several receptor tyrosine kinases, including vascular endothelial growth factor receptor2, platelet-derived growth factor receptor. Epithelial mesenchymal transition (EMT) describes a process wherein static epithelial cells lose cell-cell contacts, acquire mesenchymal features and manifest a migratory phenotype, mediating malignant phenotypes for cancer cells. It remains unclear for involvement of Sorafenib against EMT, especially in hepatocellular carcinoma (HCC). Hepatocyte growth factor (HGF) activated HGF/MET signaling pathway in HepG2 and Huh7 cells and resulted in cell scattering and spindle-shaped morphology, changes that are characteristic of EMT. SNAI1 is a key transcription factor known to be involved in EMT. HGF up-regulated SNAI1 and N-cadherin expression, and down-regulated E-cadherin in a dose- and time-dependent manner. Knockdown of SNAI1 by siRNA almost completely inhibited these morphological changes, indicating that SNAI1 was required for HGF-induced EMT in HCC cell lines. Similarly, Sorafenib and the MEK inhibitor U0126 markedly inhibited the HGF-induced SNAI1 expression and these morphological changes at 10 μM of concentration, whereas PI3 kinase inhibitor Wortmannin did not. In conclusion, Sorafenib exerts a potent inhibitory activity against EMT via ERK/SNAI1 in HCC. This activity may provide an additional clinical benefit in patients with HCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2296.
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