TY - JOUR AB - 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. AD - Department of Dermatology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China AU - Fang,Hong AU - Wang,Yina AU - Xu,Lina AU - Zhou,Sha AU - Bai,Juan AU - Wu,Yinhua AU - Qiao,Jianjun AU - Jiang,Xiaoling AU - Zhu,Dingxian AU - Ding,Yingguo DA - 2019/03/01 DO - 10.3892/ijmm.2018.4046 EP - 1530 IS - 3 JO - Int J Mol Med KW - gefitinib epidermal growth factor receptor signaling pathway barrier function claudins skin toxicity PY - 2019 SN - 1107-3756 1791-244X SP - 1522 ST - EGFR inhibitor gefitinib regulates barrier function in human epidermal keratinocytes via the modulation of the expression of claudins T2 - International Journal of Molecular Medicine TI - EGFR inhibitor gefitinib regulates barrier function in human epidermal keratinocytes via the modulation of the expression of claudins UR - https://doi.org/10.3892/ijmm.2018.4046 VL - 43 ER -