miRNA-181b increases the sensitivity of pancreatic ductal adenocarcinoma cells to gemcitabine in vitro and in nude mice by targeting BCL-2

  • Authors:
    • Baobao Cai
    • Yong An
    • Nan Lv
    • Jianmin Chen
    • Min Tu
    • Jie Sun
    • Pengfei Wu
    • Jishu Wei
    • Kuirong Jiang
    • Yi Miao
  • View Affiliations

  • Published online on: February 21, 2013     https://doi.org/10.3892/or.2013.2297
  • Pages: 1769-1776
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Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease and is usually resistant to chemotherapy. MicroRNA‑181b (miR-181b) has been reported to be associated with chemoresistance in various types of cancer. In this study, we investigated the effects of miR-181b on the chemosensitivity of PDAC cells to gemcitabine and the underlying molecular events. miR-181b mimics and inhibitors were synthesized for transient gene transfection in vitro. Lentivirus carrying miR-181b mimics were used to infect PDAC cells for nude mouse xenograft assays by implanting infected PDAC cells into recipient mice. Cell viability was determined by MTT assays, while gene expression was assessed using qRT-PCR, western blot analysis and enzyme-linked immunosorbent assay (ELISA). miR-181b targeting BCL-2 expression was assessed by a dual-luciferase activity assay. The data showed that miRNA-181b expression sensitized PDAC cells to gemcitabine treatment. Although gemcitabine-resistant PDAC cell sublines (SW1990/GR and CFPAC-1/GR) expressed higher levels of miRNA-181b, gemcitabine induced higher levels of apoptosis in PDAC cells transfected with miRNA-181b mimics. The nude mouse xenograft assay data showed that miR-181b transfection also sensitized the cells to gemcitabine treatment in vivo. Molecularly, bioinformatics data predicted that miR-181b was able to bind to BCL-2 mRNA 3'UTR. The dual luciferase activity assay revealed that miRNA-181b downregulated BCL-2 expression. The results from western blot analysis showed a reduced BCL-2 expression following miR-181b transfection but an enhanced caspase-3 activity in miRNA-181b mimic-transfected PDAC cells. This study demonstrates that miRNA-181b sensitizes PDAC cells to gemcitabine by targeting BCL-2.
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May 2013
Volume 29 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Cai B, An Y, Lv N, Chen J, Tu M, Sun J, Wu P, Wei J, Jiang K, Miao Y, Miao Y, et al: miRNA-181b increases the sensitivity of pancreatic ductal adenocarcinoma cells to gemcitabine in vitro and in nude mice by targeting BCL-2. Oncol Rep 29: 1769-1776, 2013
APA
Cai, B., An, Y., Lv, N., Chen, J., Tu, M., Sun, J. ... Miao, Y. (2013). miRNA-181b increases the sensitivity of pancreatic ductal adenocarcinoma cells to gemcitabine in vitro and in nude mice by targeting BCL-2. Oncology Reports, 29, 1769-1776. https://doi.org/10.3892/or.2013.2297
MLA
Cai, B., An, Y., Lv, N., Chen, J., Tu, M., Sun, J., Wu, P., Wei, J., Jiang, K., Miao, Y."miRNA-181b increases the sensitivity of pancreatic ductal adenocarcinoma cells to gemcitabine in vitro and in nude mice by targeting BCL-2". Oncology Reports 29.5 (2013): 1769-1776.
Chicago
Cai, B., An, Y., Lv, N., Chen, J., Tu, M., Sun, J., Wu, P., Wei, J., Jiang, K., Miao, Y."miRNA-181b increases the sensitivity of pancreatic ductal adenocarcinoma cells to gemcitabine in vitro and in nude mice by targeting BCL-2". Oncology Reports 29, no. 5 (2013): 1769-1776. https://doi.org/10.3892/or.2013.2297