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Ad-p53 enhances the sensitivity of triple-negative breast cancer MDA-MB-468 cells to the EGFR inhibitor gefitinib

  • Authors:
    • Xinzhao Wang
    • Hongkuan Song
    • Qian Yu
    • Qi Liu
    • Leilei Wang
    • Zhaoyun Liu
    • Zhiyong Yu
  • View Affiliations / Copyright

    Affiliations: School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Shandong Cancer Hospital, Jinan, Shandong 250117, P.R. China, Juxian Hospital of Traditional Chinese Medicine, Rizhao, Shandong 276500, P.R. China, Department of Biology, Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA, Shandong Cancer Hospital, Jinan, Shandong 250117, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 526-532
    |
    Published online on: December 11, 2014
       https://doi.org/10.3892/or.2014.3665
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Abstract

Triple-negative breast cancer (TNBC) accounts for 20% of all molecular subtypes of breast cancer. Neither endocrine nor anti-HER2 molecular targeting treatment yield promising results. At present, epidermal growth factor receptor (EGFR) inhibitor, as a single agent, is unable to obtain encouraging results in the treatment of TNBC, even though most of these tumors overexpress EGFR. In the present study, we used recombinant human p53 adenovirus (Ad-p53) and EGFR inhibitor gefitinib to treat the TNBC cell line MDA-MB-468. The combined treatment of gefitinib and Ad-p53 synergistically inhibited the proliferation of MDA-MB-468 cells; it restrained colony formation, enhanced cellular apoptosis and arrested the cell cycle in vitro, and decreased tumor burden of xenografts in nude mice. Western blot analysis revealed that Ad-p53 and gefitinib in combination significantly downregulated the phosphorylation of protein kinase B (p-Akt) and upregulated caspase-9 and cleaved caspase-3, while there were minimal effects on the expression of extracellular signal-regulated kinase (ERK) and phosphorylation of ERK (p-ERK). These results suggest that Ad-p53 may block the PI3K/Akt pathway rather than the Raf/MEK/ERK pathway. Importantly, wild-type p53 was able to reverse the drug resistance of MDA-MB-468 cells to gefitinib through inactivation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. The apoptotic activity induced by this combined treatment may be regulated by caspase cascade-dependent activation.
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Copy and paste a formatted citation
Spandidos Publications style
Wang X, Song H, Yu Q, Liu Q, Wang L, Liu Z and Yu Z: Ad-p53 enhances the sensitivity of triple-negative breast cancer MDA-MB-468 cells to the EGFR inhibitor gefitinib. Oncol Rep 33: 526-532, 2015.
APA
Wang, X., Song, H., Yu, Q., Liu, Q., Wang, L., Liu, Z., & Yu, Z. (2015). Ad-p53 enhances the sensitivity of triple-negative breast cancer MDA-MB-468 cells to the EGFR inhibitor gefitinib. Oncology Reports, 33, 526-532. https://doi.org/10.3892/or.2014.3665
MLA
Wang, X., Song, H., Yu, Q., Liu, Q., Wang, L., Liu, Z., Yu, Z."Ad-p53 enhances the sensitivity of triple-negative breast cancer MDA-MB-468 cells to the EGFR inhibitor gefitinib". Oncology Reports 33.2 (2015): 526-532.
Chicago
Wang, X., Song, H., Yu, Q., Liu, Q., Wang, L., Liu, Z., Yu, Z."Ad-p53 enhances the sensitivity of triple-negative breast cancer MDA-MB-468 cells to the EGFR inhibitor gefitinib". Oncology Reports 33, no. 2 (2015): 526-532. https://doi.org/10.3892/or.2014.3665
Copy and paste a formatted citation
x
Spandidos Publications style
Wang X, Song H, Yu Q, Liu Q, Wang L, Liu Z and Yu Z: Ad-p53 enhances the sensitivity of triple-negative breast cancer MDA-MB-468 cells to the EGFR inhibitor gefitinib. Oncol Rep 33: 526-532, 2015.
APA
Wang, X., Song, H., Yu, Q., Liu, Q., Wang, L., Liu, Z., & Yu, Z. (2015). Ad-p53 enhances the sensitivity of triple-negative breast cancer MDA-MB-468 cells to the EGFR inhibitor gefitinib. Oncology Reports, 33, 526-532. https://doi.org/10.3892/or.2014.3665
MLA
Wang, X., Song, H., Yu, Q., Liu, Q., Wang, L., Liu, Z., Yu, Z."Ad-p53 enhances the sensitivity of triple-negative breast cancer MDA-MB-468 cells to the EGFR inhibitor gefitinib". Oncology Reports 33.2 (2015): 526-532.
Chicago
Wang, X., Song, H., Yu, Q., Liu, Q., Wang, L., Liu, Z., Yu, Z."Ad-p53 enhances the sensitivity of triple-negative breast cancer MDA-MB-468 cells to the EGFR inhibitor gefitinib". Oncology Reports 33, no. 2 (2015): 526-532. https://doi.org/10.3892/or.2014.3665
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