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Article

Lapatinib inhibits the activation of NF-κB through reducing phosphorylation of IκB-α in breast cancer cells

  • Authors:
    • Chuandong Ma
    • Wenshu Zuo
    • Xingwu Wang
    • Ling Wei
    • Qian Guo
    • Xianrang Song
  • View Affiliations / Copyright

    Affiliations: Breast Oncology Centre, Shandong Tumor Hospital and Institute, Shandong Academy of Medical Sciences, Jinan 250117, P.R. China, Basic Research Centre, Shandong Tumor Hospital and Institute, Shandong Academy of Medical Sciences, Jinan 250117, P.R. China
  • Pages: 812-818
    |
    Published online on: November 29, 2012
       https://doi.org/10.3892/or.2012.2159
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Abstract

Lapatinib is highly active against breast cancer with HER2 overexpression in preclinical and clinical settings. Constitutive activation of NF-κB is linked to proliferation and apoptosis in breast cancer cells. NF-κB can be activated by HER2 in breast cancer cells. However, the effect of lapatinib on NF-κB activity is not completely clear. In this study, we showed that lapatinib potently inhibited activation of NF-κB in HER2-overexpressing breast cancer cells, including SKBR3 and MDA-MB-453; but not in non-HER2-overexpressing breast cancer cells, MDA-MB-231, MDA-MB-468 and MDA-MB‑435. In addition, we established a model of acquired resistance to lapatinib by chronically challenging SKBR3 breast cancer cells with increasing concentrations of lapatinib. EMSA assays showed that there was decreased NF-κB activity in the resistant cells. Western blot analysis showed that lapatinib reduced the phosphorylation of IκB-α in a time- and dose-dependent manner in SKBR3 cells. Furthermore, the expression level of p-IκB-α protein was markedly decreased in the resistant cells, compared with the parental SKBR3 cells. Additionally, treatment with the PI3K inhibitor LY294002 dramatically inhibited activation of NF-κB in HER2-overexpressing breast cancer cells. Moreover, LY294002 inhibited phosphorylation of Akt and IκB-α in SKBR3 cells. Our results suggest that lapatinib potently inhibits the activation of NF-κB in HER2-overexpressing breast cancer cells. Lapatinib appears to inactivate NF-κB through reducing phosphorylation of IκB-α via blocking the PI3K/Akt cascade.
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Copy and paste a formatted citation
Spandidos Publications style
Ma C, Zuo W, Wang X, Wei L, Guo Q and Song X: Lapatinib inhibits the activation of NF-κB through reducing phosphorylation of IκB-α in breast cancer cells. Oncol Rep 29: 812-818, 2013.
APA
Ma, C., Zuo, W., Wang, X., Wei, L., Guo, Q., & Song, X. (2013). Lapatinib inhibits the activation of NF-κB through reducing phosphorylation of IκB-α in breast cancer cells. Oncology Reports, 29, 812-818. https://doi.org/10.3892/or.2012.2159
MLA
Ma, C., Zuo, W., Wang, X., Wei, L., Guo, Q., Song, X."Lapatinib inhibits the activation of NF-κB through reducing phosphorylation of IκB-α in breast cancer cells". Oncology Reports 29.2 (2013): 812-818.
Chicago
Ma, C., Zuo, W., Wang, X., Wei, L., Guo, Q., Song, X."Lapatinib inhibits the activation of NF-κB through reducing phosphorylation of IκB-α in breast cancer cells". Oncology Reports 29, no. 2 (2013): 812-818. https://doi.org/10.3892/or.2012.2159
Copy and paste a formatted citation
x
Spandidos Publications style
Ma C, Zuo W, Wang X, Wei L, Guo Q and Song X: Lapatinib inhibits the activation of NF-κB through reducing phosphorylation of IκB-α in breast cancer cells. Oncol Rep 29: 812-818, 2013.
APA
Ma, C., Zuo, W., Wang, X., Wei, L., Guo, Q., & Song, X. (2013). Lapatinib inhibits the activation of NF-κB through reducing phosphorylation of IκB-α in breast cancer cells. Oncology Reports, 29, 812-818. https://doi.org/10.3892/or.2012.2159
MLA
Ma, C., Zuo, W., Wang, X., Wei, L., Guo, Q., Song, X."Lapatinib inhibits the activation of NF-κB through reducing phosphorylation of IκB-α in breast cancer cells". Oncology Reports 29.2 (2013): 812-818.
Chicago
Ma, C., Zuo, W., Wang, X., Wei, L., Guo, Q., Song, X."Lapatinib inhibits the activation of NF-κB through reducing phosphorylation of IκB-α in breast cancer cells". Oncology Reports 29, no. 2 (2013): 812-818. https://doi.org/10.3892/or.2012.2159
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