Department of Biomolecular Pharmacology, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
Biomolecules. 2020 Apr 3;10(4):545. doi: 10.3390/biom10040545.
An adverse reaction of dry skin occurs frequently during treatment with anticancer epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). In this study, we conducted basic research to clarify the mechanism of EGFR-TKI-induced dry skin and propose new treatments or preventative measures. Dermal water content was significantly lower in the erlotinib-treated mice than in the control group. An assessment of the expression levels of functional genes in the skin revealed that only the expression of the water channel aquaporin-3 (AQP3) was significantly decreased in the erlotinib-treated group. When erlotinib was added to epidermal keratinocyte HaCaT cells, the expression levels of both AQP3 mRNA and protein decreased. Erlotinib treatment also significantly decreased the expression levels of phospho-EGFR and phospho-extracellular signal-regulated kinase (ERK), both in HaCaT cells and mouse skin. Dry skin due to erlotinib may be caused by the decreased expression of AQP3 in the skin, thereby limiting water transport from the vascular side to the corneum side. The decrease in AQP3 may also be attributable to ERK suppression via inhibition of EGFR activity by erlotinib. Therefore, substances that increase AQP3 expression may be effective for erlotinib-induced dry skin.
在使用抗癌表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）治疗期间，常发生皮肤干燥不良反应。本研究进行了基础研究，以阐明 EGFR-TKI 诱导皮肤干燥的机制，并提出新的治疗或预防措施。与对照组相比，厄洛替尼治疗组小鼠的皮肤水分含量明显降低。对皮肤中功能基因表达水平的评估表明，仅在厄洛替尼治疗组中，水通道蛋白 3（AQP3）的表达明显降低。当厄洛替尼被添加到表皮角质形成细胞 HaCaT 细胞中时，AQP3 mRNA 和蛋白的表达水平均降低。厄洛替尼治疗还显著降低了 HaCaT 细胞和小鼠皮肤中磷酸化 EGFR 和磷酸化细胞外信号调节激酶（ERK）的表达水平。厄洛替尼引起的皮肤干燥可能是由于皮肤中 AQP3 的表达减少，从而限制了水从血管侧向角质层侧的转运。AQP3 的减少也可能归因于 ERK 抑制，这是通过厄洛替尼抑制 EGFR 活性引起的。因此，增加 AQP3 表达的物质可能对厄洛替尼引起的皮肤干燥有效。
