Effects of Irisin Combined with Gefitinib on Expression Levels of miRNAs in the HepG2 Cell Line

Abstract

This study aims to investigate the effects of the combination of irisin and gefitinib on the expression of AKT1, FNCD5, VEGF, Bcl-2, EGFR, PI3K, CDK1, and ERBB2 genes, which play critical roles in the pathogenesis of hepatocellular carcinoma, beside the expression of miRNAs targeting these genes in the HepG2 cell line. MTT assay was applied to evaluate the cytotoxicity induced by irisin or gefitinib. Expressions of miR- 664b-5p, miR-3922-5p, miR-6843-3p, miR- 8085, miR-381-5p, miR-1275, miR-1304, and miR-6801-5p, and the expression of target genes of these miRNAs were determined by RT-PCR. The most effective time for the combination of irisin and gefitinib in HepG2 cells was 48 hours, and the dose was 3.125 μM for irisin and 10.34 μM for gefitinib. PI3K, Akt, EGF, and ErbB2 expressions were significantly decreased in irisin groups compared to the control group. We found that irisin alone and in combination with gefitinib increased miR-664b-5p, miR-381-5p, miR-3922-5p, miR-1275, and miR-1304 gene expressions, whereas the combined treatment of irisin with gefitinib decreased miR-8085 expression. Our study shows that irisin can enhance the anticancer effects of gefitinib in the HepG2 cell line and dysregulated miRNA expressions contribute to HCC pathogenesis by decreasing cell proliferation and inducing apoptosis.