MiR-17-5p Inhibitor Enhances Chemosensitivity to Gemcitabine Via Upregulating Bim Expression in Pancreatic Cancer Cells

Abstract

miR-17-5p is reported to be overexpressed in pancreatic cancer, and it plays an important role in carcinogenesis and cancer progression. Gemcitabine is the standard first-line chemotherapeutic agent for pancreatic cancer, however the chemoresistance limits the curative effect. In the present study, we investigated whether inhibition of miR-17-5p could enhance chemosensitivity to gemcitabine in pancreatic cancer cells. miR-17-5p inhibitor was transfected to pancreatic cancer cell lines Panc-1 and BxPC3, and then cell proliferation, cell apoptosis, caspase-3 activation, and chemosensitivity to gemcitabine were measured in vitro. Our data showed that Panc-1 and BxPC3 cells transfected with miR-17-5p inhibitor showed growth inhibition, spontaneous apoptosis, higher caspase-3 activation, and increased chemosensitivity to gemcitabine. In addition, miR-17-5p inhibitor upregulated Bim protein expression in a dose-dependent manner without changing the Bim mRNA level, and it increased the activity of a luciferase reporter construct containing the Bim-3' untranslated region. These results prove that miR-17-5p negatively regulates Bim at the posttranscriptional level. We suggest that miR-17-5p inhibitor gene therapy would be a novel approach to chemosensitization for human pancreatic cancer.