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

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Abstract

Background

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.

Aims

In the present study, we investigated whether inhibition of miR-17-5p could enhance chemosensitivity to gemcitabine in pancreatic cancer cells.

Methods

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.

Results

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.

Conclusions

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.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (Grant 81201676, 30972703, 81171653), and the science and technology project for young talent by Changzhou Municipal Health Bureau (Grant QN201103).

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, People’s Republic of China

    Hai-jiao Yan, Wen-hui Sun, Jun Wu, Mei Ji, Qi Wang, Xiao Zheng, Jing-ting Jiang & Chang-ping Wu

  2. Department of Hepatobiliary Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, People’s Republic of China

    Wen-song Liu

Authors
  1. Hai-jiao Yan
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  2. Wen-song Liu
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  3. Wen-hui Sun
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  4. Jun Wu
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  5. Mei Ji
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  6. Qi Wang
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  7. Xiao Zheng
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  8. Jing-ting Jiang
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  9. Chang-ping Wu
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Corresponding authors

Correspondence to Jing-ting Jiang or Chang-ping Wu.

Additional information

Hai-jiao Yan and Wen-song Liu contributed equally to this study.

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Yan, Hj., Liu, Ws., Sun, Wh. et al. miR-17-5p Inhibitor Enhances Chemosensitivity to Gemcitabine Via Upregulating Bim Expression in Pancreatic Cancer Cells. Dig Dis Sci 57, 3160–3167 (2012). https://doi.org/10.1007/s10620-012-2400-4

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  • DOI: https://doi.org/10.1007/s10620-012-2400-4

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