EGFR inhibitor gefitinib regulates barrier function in human epidermal keratinocytes via the modulation of the expression of claudins

  • Authors:
    • Hong Fang
    • Yina Wang
    • Lina Xu
    • Sha Zhou
    • Juan Bai
    • Yinhua Wu
    • Jianjun Qiao
    • Xiaoling Jiang
    • Dingxian Zhu
    • Yingguo Ding
  • View Affiliations

  • Published online on: December 31, 2018     https://doi.org/10.3892/ijmm.2018.4046
  • Pages: 1522-1530
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Abstract

Gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, has been frequently used in targeted therapy for lung cancer. However, the widespread use of gefitinib in targeted therapy for patients with lung cancer is hampered by its common skin toxicities. The present study aimed to investigate the mechanisms underlying the skin toxicities of gefitinib. Normal human epidermal keratinocytes (NHEKs) treated with gefitinib were used for a series of in vitro assays, including MTT, reverse transcription‑quantitative polymerase chain reaction, western blot analysis, immunohistochemistry and transepithelial electrical resistance and paracellular permeability detection. In the present study, it was determined that the skin toxicities of gefitinib may be due to claudin (CLDN)1 and CLDN4 downregulation and CLDN2 upregulation in NHEKs. Additionally, Src and signal transducer and activator of transcription 3 pathways were involved in gefitinib‑induced barrier function disruption in NHEKs. In conclusion, the present study may provide novel insights for improving skin toxicity of gefitinib in patients with lung cancer.

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Copy and paste a formatted citation
APA
Fang, H., Wang, Y., Xu, L., Zhou, S., Bai, J., Wu, Y. ... Ding, Y. (2019). EGFR inhibitor gefitinib regulates barrier function in human epidermal keratinocytes via the modulation of the expression of claudins. International Journal of Molecular Medicine, 43, 1522-1530. https://doi.org/10.3892/ijmm.2018.4046
MLA
Fang, H., Wang, Y., Xu, L., Zhou, S., Bai, J., Wu, Y., Qiao, J., Jiang, X., Zhu, D., Ding, Y."EGFR inhibitor gefitinib regulates barrier function in human epidermal keratinocytes via the modulation of the expression of claudins". International Journal of Molecular Medicine 43.3 (2019): 1522-1530.
Chicago
Fang, H., Wang, Y., Xu, L., Zhou, S., Bai, J., Wu, Y., Qiao, J., Jiang, X., Zhu, D., Ding, Y."EGFR inhibitor gefitinib regulates barrier function in human epidermal keratinocytes via the modulation of the expression of claudins". International Journal of Molecular Medicine 43, no. 3 (2019): 1522-1530. https://doi.org/10.3892/ijmm.2018.4046