miR-378a enhances the sensitivity of liver cancer to sorafenib by targeting VEGFR, PDGFR[beta] and c-Raf

Liver cancer is a globally prevalent cancer with poor prognosis. The present study investigated the link between microRNA-378a (miR-378a) expression and the sensitivity of hepatocellular carcinoma (HCC) and hepatoblastoma (HB) cancers to sorafenib therapy. miR-378a expression was determined in liver tissue samples from healthy candidates and patients with liver cancer using the reverse transcription-quantitative polymerase chain reaction. The antitumor effects of miR-378a alone and in combination with sorafenib were investigated in the HB cell line HepG2 and the HCC cell line SMMC-7721 with methyl thiazoyl tetrazolium, colony formation, flow cytometry and Transwell migration assays. The underlying mechanisms were investigated using western blot analysis. miR-378a expression was decreased in tissue samples from patients with liver cancer. HCC and HB cell line proliferation and invasion ability was inhibited by miR-378a. The combination of miR-378a and sorafenib provided the greatest inhibition. Western blot indicated that mitogen activated protein kinase signaling pathway proteins, vascular endothelial growth factor receptor, platelet derived growth factor receptor [beta], Raf-1 proto-oncogene, serine/threonine kinase and matrix metallopeptidase 2 were regulated by miR-378a alone and to a greater extent when combined with sorafenib. Results suggest that miR-378a can inhibit liver cancer cell growth and enhance the sensitivity of liver cancer cells to sorafenib-based chemotherapies. Key words: hepatocellular carcinoma, hepatoblastoma, microRNA-378a, proliferation, invasion, sorafenib