Open Access

Paclitaxel resistance is mediated by NF‑κB on mesenchymal primary breast cancer cells

  • Authors:
    • José Esparza‑López
    • Ossian Longoria
    • Eliseo Neftali De La Cruz‑Escobar
    • Julio Cesar Garibay‑Díaz
    • Eucario León‑Rodríguez
    • María De Jesús Ibarra‑Sánchez
  • View Affiliations

  • Published online on: December 16, 2021     https://doi.org/10.3892/ol.2021.13168
  • Article Number: 50
  • Copyright: © Esparza‑López et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Paclitaxel has been used widely to treat breast cancer and other types of cancer. However, resistance is a major cause of failure for treatment and results in cancer progression. The present study investigated the association between paclitaxel resistance and the mesenchymal phenotype, using a model of primary breast cancer cells and employing four different cultures, two with an epithelial phenotype (MBCDF and MBCD17) and two with a mesenchymal phenotype (MBCDF‑D5 and MBCD3). Epithelial‑mesenchymal markers were evaluated by western blotting; MBCDF and MBCD17 cells expressed E‑cadherin, SNAIL, Slug, and Twist, low levels of N‑cadherin, but not vimentin. MBCDF‑D5 and MBCD3 cells expressed N‑cadherin, vimentin, and higher levels of SNAIL, and low levels of E‑cadherin, Slug, and Twist. Cell viability was evaluated using a crystal violet assay after paclitaxel treatment; primary breast cancer cells with mesenchymal phenotype were resistant to paclitaxel compared with the epithelial primary breast cancer cells. Furthermore, using western blotting, it was revealed that mesenchymal cells had elevated levels of nuclear factor‑κΒ (NF‑κB) p65 and IκB kinase (IKK). Additionally, it was demonstrated that paclitaxel‑induced degradation of the inhibitor of NF‑κB, activation of NF‑κB in a dose‑dependent manner, and Bcl‑2 and Bcl‑xL upregulation. Finally, employing western blotting and crystal violet assays, the effects of the proteasome inhibitor ALLN were assessed. ALLN inhibited paclitaxel‑induced NF‑κB activation and restored the sensitivity to paclitaxel. Together, these data suggest that targeting the NF‑κB/IKK axis might be a promising strategy to overcome paclitaxel resistance.
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February-2022
Volume 23 Issue 2

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Esparza‑López J, Longoria O, De La Cruz‑Escobar EN, Garibay‑Díaz JC, León‑Rodríguez E and Ibarra‑Sánchez MD: Paclitaxel resistance is mediated by NF‑κB on mesenchymal primary breast cancer cells. Oncol Lett 23: 50, 2022
APA
Esparza‑López, J., Longoria, O., De La Cruz‑Escobar, E.N., Garibay‑Díaz, J.C., León‑Rodríguez, E., & Ibarra‑Sánchez, M.D. (2022). Paclitaxel resistance is mediated by NF‑κB on mesenchymal primary breast cancer cells. Oncology Letters, 23, 50. https://doi.org/10.3892/ol.2021.13168
MLA
Esparza‑López, J., Longoria, O., De La Cruz‑Escobar, E. N., Garibay‑Díaz, J. C., León‑Rodríguez, E., Ibarra‑Sánchez, M. D."Paclitaxel resistance is mediated by NF‑κB on mesenchymal primary breast cancer cells". Oncology Letters 23.2 (2022): 50.
Chicago
Esparza‑López, J., Longoria, O., De La Cruz‑Escobar, E. N., Garibay‑Díaz, J. C., León‑Rodríguez, E., Ibarra‑Sánchez, M. D."Paclitaxel resistance is mediated by NF‑κB on mesenchymal primary breast cancer cells". Oncology Letters 23, no. 2 (2022): 50. https://doi.org/10.3892/ol.2021.13168