MiR‑378a enhances the sensitivity of liver cancer to sorafenib by targeting VEGFR, PDGFRβ and c‑Raf.

Abstract

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 receptorβ, Raf‑1 proto‑oncogene, serine/threonine kinase and matrix metallopeptidase2 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.