Fenofibrate suppresses the progression of hepatoma by inhibiting PI3K/AKT/Twist pathway through downregulating Osteopontin

Abstract

Abstract Primary hepatic carcinoma (PHC) is a leading threat to cancer patients with few effective treatment strategies. OPN is found to be an oncogene in hepatocellular carcinoma (HCC) with potential as a treating target for PHC. Fenofibrate is a lipid-lowering drug with potential anti-tumor properties, which is claimed with suppressive effects on OPN expression. Our study proposes to explore the molecular mechanism of fenofibrate in inhibiting HCC. OPN was found extremely upregulated in 3 HCC cell lines, especially Hep3B cells. Hep3B cells were treated with 75 and 100 µM Fenofibrate, while OPN-overexpressed Hep3B cells were treated with 100 µM Fenofibrate. Hep3B xenograft model was established, followed by treated with 100 mg/kg and 200 mg/kg Fenofibrate. OPN-overexpressed Hep3B xenograft model was established, followed by treated with 200 mg/kg Fenofibrate. Decreased clone number, elevated apoptotic rate, reduced number of migrated cells, shortened migration distance, and suppressed tumor growth in xenograft model were observed by the administration of Fenofibrate, which were markedly abolished by the overexpression of OPN. Furthermore, the inhibitory effect of Fenofibrate on the PI3K/AKT/Twist pathway in Hep3B cells and Hep3B xenograft model was abrogated by OPN overexpression. Collectively, Fenofibrate suppressed progression of hepatoma by inhibiting PI3K/AKT/Twist pathway through downregulating OPN.