BRD4 promotes pancreatic ductal adenocarcinoma cell proliferation and enhances gemcitabine resistance

  • Authors:
    • Yong-Hui Wang
    • Ya-Na Sui
    • Kai Yan
    • Li-Shan Wang
    • Fei Wang
    • Jia-Hua Zhou
  • View Affiliations

  • Published online on: January 30, 2015     https://doi.org/10.3892/or.2015.3774
  • Pages: 1699-1706
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Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive carcinoma with a poor prognosis. To date, there is no effective treatment for this fatal disease. The manipulation of epigenetic proteins, such as BRD4, has recently emerged as an alternative therapeutic strategy. Our objective was to analyze the effect of BRD4 on the cell progression and chemoresistance of PDAC and the novel mechanisms involved. In the present study, we firstly revealed that the expression of BRD4 was significantly upregulated in PDAC cell lines, compared to that in human pancreatic duct epithelial cells. An in vitro assay showed that the suppression of BRD4 impaired PDAC cell viability and proliferation. Similarly, the tumor growth rate was also decreased in vivo after silencing of BRD4. Furthermore, we showed that the expression of BRD4 was increased after treatment with gemcitabine (GEM). Combination treatment of GEM and BRD4 silencing had a synergistic effect on the chemotherapeutic efficacy in the PANC-1 and MIAPaCa-2 cell lines, and significantly promoted apoptosis. In particular, we demonstrated that BRD4 activated the Sonic hedgehog (Shh) signaling pathway members in a ligand-independent manner in the PDAC cells. Together, our results indicate the important role of BRD4 in PDAC cell proliferation and chemoresistance and suggests that BRD4 is a promising target directed against the transcriptional program of PDAC.
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April-2015
Volume 33 Issue 4

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

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Spandidos Publications style
Wang Y, Sui Y, Yan K, Wang L, Wang F and Zhou J: BRD4 promotes pancreatic ductal adenocarcinoma cell proliferation and enhances gemcitabine resistance. Oncol Rep 33: 1699-1706, 2015
APA
Wang, Y., Sui, Y., Yan, K., Wang, L., Wang, F., & Zhou, J. (2015). BRD4 promotes pancreatic ductal adenocarcinoma cell proliferation and enhances gemcitabine resistance. Oncology Reports, 33, 1699-1706. https://doi.org/10.3892/or.2015.3774
MLA
Wang, Y., Sui, Y., Yan, K., Wang, L., Wang, F., Zhou, J."BRD4 promotes pancreatic ductal adenocarcinoma cell proliferation and enhances gemcitabine resistance". Oncology Reports 33.4 (2015): 1699-1706.
Chicago
Wang, Y., Sui, Y., Yan, K., Wang, L., Wang, F., Zhou, J."BRD4 promotes pancreatic ductal adenocarcinoma cell proliferation and enhances gemcitabine resistance". Oncology Reports 33, no. 4 (2015): 1699-1706. https://doi.org/10.3892/or.2015.3774