MiR-1 reverses multidrug resistance in gastric cancer cells via downregulation of sorcin through promoting the accumulation of intracellular drugs and apoptosis of cells

Abstract

Gastric cancer (GC) is one of the most common cancers worldwide and results in the second greatest rate of cancer-associated mortality globally. Multidrug resistance (MDR) often develops during the chemotherapy, resultinginthefailureoftreatment.Toinvestigatethemolecular mechanism of MDR, the roles of microRNA (miR)-1 were studied in GC. Reverse transcription-quantitative polymerase chain reaction and western blotting were used to investigate the expression levels of miR-1 and sorcin in SGC7901/ADM and SGC7901/VCR cell lines. The effect of miR-1 on the half maximal inhibitory concentration (IC50), cell apoptosis rates and drug accumulation was uncovered by MTT assay and flow cytometric analysis. Furthermore, dual-luciferase assay and western blotting were used to determine the target of miR-1 in GC. It was demonstrated that miR-1 was highly downregulated in MDR GC cell lines, including SGC7901/ADM and SGC7901/VCR. Overexpression of miR-1 in MDR GC cells decreased IC50, but increased the cell apoptosis rates and promoted the drug accumulation in cancer cells. Dual-luciferase activity assay indicated that sorcin was the target of miR-1 in GC. In addition, overexpression of sorcin could partially reverse the effect of miR-1 in MDR GC cells. The role of miR-1 in MDR GC cells makes it a potential therapeutic target for a successful clinical outcome.