EGFR/HER2 inhibitors effectively reduce the malignant potential of MDR breast cancer evoked by P-gp substrates in vitro and in vivo

  • Authors:
    • Yiting Jin
    • Wei Zhang
    • Hongying Wang
    • Zijing Zhang
    • Chengyu Chu
    • Xiuping Liu
    • Qiang Zou
  • View Affiliations

  • Published online on: November 25, 2015     https://doi.org/10.3892/or.2015.4444
  • Pages: 771-778
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Abstract

Multidrug resistance (MDR) induced by chemotherapy in breast cancer frequently leads to tumor invasion, metastasis and poor clinical outcome. We preliminarily found that the epidermal growth factor receptor (EGFR) is involved in enhancing the malignant potential of MDR breast cancer cells, but the mechanism remains unclear. In the present study, we demonstrated in vitro and in vivo that EGFR/HER2 promote the invasive and metastatic abilities of MDR breast cancer. More importantly, a new function of EGFR/HER2 inhibitors was revealed for the first time, which could improve the treatment efficacy of breast cancer by reversing the MDR process rather than by inhibiting tumor growth. Firstly, using quantitative real‑time PCR and western blot analysis, we found that overexpression of EGFR/HER2 in MCF7/Adr cells upregulated CD147 and MMP2/9 at both the transcription and protein expression levels, which promoted tumor cell migration, as determined using an in vitro invasion assay. Secondly, the upregulated levels of CD147 and MMP2/9 were decreased when EGFR/HER2 activity was inhibited, and therefore tumor invasion was also significantly inhibited. These phenomena were also demonstrated in nude mouse assays. Additionally, in MDR breast cancer patients, we found that overexpression of EGFR and P‑gp levels led to shorter overall survival (OS) and disease‑free survival (DFS) by IHC assays and Kaplan‑Meier survival analysis. In conclusion, EGFR/HER2 play a crucial role in enhancing CD147 and MMP expression to establish favorable conditions for invasion/metastasis in MDR breast cancer. The scope of application of EGFR/HER2 inhibitors may be expanded in EGFR/HER2‑positive patients. We suggest that MDR breast cancer patients may benefit from novel therapies targeting EGFR/HER2.
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February-2016
Volume 35 Issue 2

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

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Spandidos Publications style
Jin Y, Zhang W, Wang H, Zhang Z, Chu C, Liu X and Zou Q: EGFR/HER2 inhibitors effectively reduce the malignant potential of MDR breast cancer evoked by P-gp substrates in vitro and in vivo. Oncol Rep 35: 771-778, 2016
APA
Jin, Y., Zhang, W., Wang, H., Zhang, Z., Chu, C., Liu, X., & Zou, Q. (2016). EGFR/HER2 inhibitors effectively reduce the malignant potential of MDR breast cancer evoked by P-gp substrates in vitro and in vivo. Oncology Reports, 35, 771-778. https://doi.org/10.3892/or.2015.4444
MLA
Jin, Y., Zhang, W., Wang, H., Zhang, Z., Chu, C., Liu, X., Zou, Q."EGFR/HER2 inhibitors effectively reduce the malignant potential of MDR breast cancer evoked by P-gp substrates in vitro and in vivo". Oncology Reports 35.2 (2016): 771-778.
Chicago
Jin, Y., Zhang, W., Wang, H., Zhang, Z., Chu, C., Liu, X., Zou, Q."EGFR/HER2 inhibitors effectively reduce the malignant potential of MDR breast cancer evoked by P-gp substrates in vitro and in vivo". Oncology Reports 35, no. 2 (2016): 771-778. https://doi.org/10.3892/or.2015.4444