MiRNA-200b reverses drug resistance of hepatocellular carcinoma HepG2 cells to sorafenib and its underlying mechanism

Abstract

Objective To explore the effect of miRNA-200b on sorafenib resistance in hepatocellular carcinoma cells in order to increase the efficacy of the drug in advanced liver cancer patients. Methods Sorafenib resistant hepatocellular carcinoma HepG2-SR cell line was established by gradually increasing the concentration of sorafenib in the culture medium. The expression of miRNA-200b in HepG2-SR cells, HepG2 cells and miRNA-200b transfected HepG2-SR cells was detected by real-time fluorescence quantitative assay (RT-PCR). In HepG2-SR cells before and after transfection, sorafenib sensitivity was detected by CCK-8 assay, migration and invasion abilities were detected by wound-healing assay and Transwell assay, cell apoptosis was measured by flow cytometry, and expression levels of epithelial mesenchymal transition (EMT) markers were studied by Western blotting. Results Sorafenib resistance was significantly higher and expression of miRNA-200b was significantly lower in HepG2-SR cells than HepG2 cells. Transfection of miRNA-200b mimics resulted in significantly increased miRNA-200b expression, decreased IC50 of sorafenib, reduced cell migration rate and cell invasion, enhanced apoptosis and increased expression of E-cadherin but decreased expression of N-cadherin and Vimentin. Conclusion MiRNA-200b reversed sorafenib resistance of HepG2-SR cells by inducing apoptosis and inhibiting cell proliferation, migration, invasion and EMT.

Keywords

• hepatocellular carcinoma
• mirna-200b
• sorafenib
• drug resistance