Abstract

Pancreatic ductal adenocarcinoma (PDAC) isa highly lethal disease and is usually resistant to chemotherapy. MicroRNA‑181b (miR-181b) has been reported to be associated withchemoresistance in various types of cancer. In this study, we investigated theeffects of miR-181b on the chemosensitivity of PDAC cells to gemcitabine andthe underlying molecular events. miR-181b mimics and inhibitors weresynthesized for transient gene transfection in vitro. Lentivirus carryingmiR-181b mimics were used to infect PDAC cells for nude mouse xenograft assaysby implanting infected PDAC cells into recipient mice. Cell viability wasdetermined by MTT assays, while gene expression was assessed using qRT-PCR,western blot analysis and enzyme-linked immunosorbent assay (ELISA). miR-181btargeting BCL-2 expression was assessed by a dual-luciferase activity assay.The data showed that miRNA-181b expression sensitized PDAC cells to gemcitabinetreatment. Although gemcitabine-resistant PDAC cell sublines (SW1990/GR andCFPAC-1/GR) expressed higher levels of miRNA-181b, gemcitabine induced higherlevels of apoptosis in PDAC cells transfected with miRNA-181b mimics. The nudemouse xenograft assay data showed that miR-181b transfection also sensitizedthe cells to gemcitabine treatment in vivo. Molecularly, bioinformatics datapredicted that miR-181b was able to bind to BCL-2 mRNA 3'UTR. The dualluciferase activity assay revealed that miRNA-181b downregulated BCL-2expression. The results from western blot analysis showed a reduced BCL-2expression following miR-181b transfection but an enhanced caspase-3 activityin miRNA-181b mimic-transfected PDAC cells. This study demonstrates thatmiRNA-181b sensitizes PDAC cells to gemcitabine by targeting BCL-2.