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

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.

journal_name

Int J Mol Med

authors

Fang H,Wang Y,Xu L,Zhou S,Bai J,Wu Y,Qiao J,Jiang X,Zhu D,Ding Y

doi

10.3892/ijmm.2018.4046

subject

Has Abstract

pub_date

2019-03-01 00:00:00

pages

1522-1530

issue

3

eissn

1107-3756

issn

1791-244X

journal_volume

43

pub_type

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