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Article

Breast cancer cells evade paclitaxel-induced cell death by developing resistance to dasatinib

  • Authors:
    • Yun‑Ji Jeong
    • Jong Soon Kang
    • Su In Lee
    • Dong Min So
    • Jieun Yun
    • Ji Young Baek
    • Sang Kyum Kim
    • Kiho Lee
    • Song‑Kyu Park
  • View Affiliations / Copyright

    Affiliations: College of Pharmacy, Korea University, Sejong 30019, Republic of Korea, Bioevaluation Center, Korea Institute of Bioscience and Biotechnology, Ochang 28116, Republic of Korea, College of Pharmacy, Chungnam National University, Daejeon 34134, Republic of Korea
  • Pages: 2153-2158
    |
    Published online on: July 13, 2016
       https://doi.org/10.3892/ol.2016.4852
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Abstract

Triple negative breast cancer (TNBC), which does not express the progesterone, estrogen, or HER2/neu receptor, is aggressive and difficult to treat. Paclitaxel, a tubulin stabilizing agent, is one of the most frequently prescribed anticancer agents for breast cancers, including TNBC. Residual disease that occurs due to resistance or partial resistance of cancer cells in a tumor against anticancer agents is the most important issue in oncology. In the present study, when MDA‑MB‑231 cells, a TNBC cell line, were treated with 30 µM paclitaxel, a slightly higher concentration than its GI50 value, for 6 days, a small number of cells with different morphologies survived. Among the surviving cells, small round cells were isolated, cloned, and named MDA‑MB‑231‑JYJ cells. MDA‑MB‑231‑JYJ cells were observed to be highly proliferative and tumorigenic. In addition, signal transduction molecules involved in proliferation, survival, malignancy, or stemness of cancer cells, such as c‑Src, c‑Met, Notch 1, c‑Myc, Sox2, Oct3/4, Nanog, and E‑cadherin were highly expressed or activated. While further study is required, MDA‑MB‑231‑JYJ cells appear to have some of the characteristics of cancer precursor cells. Although MDA‑MB‑231‑JYJ cells were isolated from the cells that survived in the continuous presence of paclitaxel, they were not resistant to paclitaxel but developed resistance to dasatinib, a Bcr‑Abl and Src kinase family inhibitor. The activated state of Src and Notch 1, and the expression levels of c‑Myc and cyclins in MDA‑MB‑231‑JYJ cells were less affected than MDA‑MB‑231 cells by the treatment of dasatinib, which may explain the resistance of MDA‑MB‑231‑JYJ cells to dasatinib. These results suggest that cancer cells that become resistant to dasatinib during the process of paclitaxel therapy in patients may appear, and caution is required in the design of clinical trials using these two agents.
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Copy and paste a formatted citation
Spandidos Publications style
Jeong YJ, Kang JS, Lee SI, So DM, Yun J, Baek JY, Kim SK, Lee K and Park SK: Breast cancer cells evade paclitaxel-induced cell death by developing resistance to dasatinib. Oncol Lett 12: 2153-2158, 2016.
APA
Jeong, Y., Kang, J.S., Lee, S.I., So, D.M., Yun, J., Baek, J.Y. ... Park, S. (2016). Breast cancer cells evade paclitaxel-induced cell death by developing resistance to dasatinib. Oncology Letters, 12, 2153-2158. https://doi.org/10.3892/ol.2016.4852
MLA
Jeong, Y., Kang, J. S., Lee, S. I., So, D. M., Yun, J., Baek, J. Y., Kim, S. K., Lee, K., Park, S."Breast cancer cells evade paclitaxel-induced cell death by developing resistance to dasatinib". Oncology Letters 12.3 (2016): 2153-2158.
Chicago
Jeong, Y., Kang, J. S., Lee, S. I., So, D. M., Yun, J., Baek, J. Y., Kim, S. K., Lee, K., Park, S."Breast cancer cells evade paclitaxel-induced cell death by developing resistance to dasatinib". Oncology Letters 12, no. 3 (2016): 2153-2158. https://doi.org/10.3892/ol.2016.4852
Copy and paste a formatted citation
x
Spandidos Publications style
Jeong YJ, Kang JS, Lee SI, So DM, Yun J, Baek JY, Kim SK, Lee K and Park SK: Breast cancer cells evade paclitaxel-induced cell death by developing resistance to dasatinib. Oncol Lett 12: 2153-2158, 2016.
APA
Jeong, Y., Kang, J.S., Lee, S.I., So, D.M., Yun, J., Baek, J.Y. ... Park, S. (2016). Breast cancer cells evade paclitaxel-induced cell death by developing resistance to dasatinib. Oncology Letters, 12, 2153-2158. https://doi.org/10.3892/ol.2016.4852
MLA
Jeong, Y., Kang, J. S., Lee, S. I., So, D. M., Yun, J., Baek, J. Y., Kim, S. K., Lee, K., Park, S."Breast cancer cells evade paclitaxel-induced cell death by developing resistance to dasatinib". Oncology Letters 12.3 (2016): 2153-2158.
Chicago
Jeong, Y., Kang, J. S., Lee, S. I., So, D. M., Yun, J., Baek, J. Y., Kim, S. K., Lee, K., Park, S."Breast cancer cells evade paclitaxel-induced cell death by developing resistance to dasatinib". Oncology Letters 12, no. 3 (2016): 2153-2158. https://doi.org/10.3892/ol.2016.4852
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