Zhang Yali, Wang Yalei, Chen Ziwei, Cheng Shuo, Ding Chengcheng, Zhang Jiani, Peng Tiantian, Chen Weihang, Zhang Dingyang, Tan Yan, Wang Xu, Dong Ruijuan, Jiang Miao, Hua Qian
Beijing University of Chinese Medicine, Sunshine South street, Fangshan district, Beijing 102488, China.
Toxicol Res (Camb). 2021 Mar 11;10(2):334-344. doi: 10.1093/toxres/tfab008. eCollection 2021 Mar.
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) such as gefitinib, erlotinib, and afatinib, are widely used in clinical practice and remarkably effective in treatment of advanced non-small cell lung cancer. However, there are some adverse effects while taking EGFR-TKIs, among which skin adverse reactions (SAR) are the most common events. At present, the poor outcome of SAR and insufficient research on SAR models need to be addressed. In this study we focused on the SAR models to lay a foundation for mechanism researches. Gefitinib, one of the EGFR-TKIs, was used as SAR inducing agents. We chose C57BL/6 and FVB/N mice as experimental model and they were divided into four groups. The weight and skin moisture of mice were detected every 7 days, itching behavior and abnormal eyelids were tested at 35th day after gavage, and survival rate was also recorded. The weight of unit area hair, length of whiskers and inflammatory cells were evaluated after mice sacrificed. C57BL/6 animals treated with gefitinib showed significant differences in survival rate, weight of unit area hair, skin moisture changes, skin dryness, itching behavior, whisker irregular growth, abnormal eyelids, and inflammatory cells; FVB/N animals treated with gefitinib only showed significant differences in survival rate, whisker irregular growth and abnormal eyelids, compared with the control group, respectively. In this study, we compared the similarities and differences of gefitinib-induced SAR between C57BL/6 and FVB/N mice, which illustrated different patients probably showing different symptoms clinically and provided experimental basis for researching mechanism of EGFR-TKIs induced SAR.
表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs),如吉非替尼、厄洛替尼和阿法替尼,在临床实践中被广泛应用,并且在治疗晚期非小细胞肺癌方面非常有效。然而,服用EGFR-TKIs时会出现一些不良反应,其中皮肤不良反应(SAR)是最常见的事件。目前,SAR的不良结果以及对SAR模型的研究不足需要得到解决。在本研究中,我们聚焦于SAR模型,为机制研究奠定基础。吉非替尼作为EGFR-TKIs之一,被用作SAR诱导剂。我们选择C57BL/6和FVB/N小鼠作为实验模型,并将它们分为四组。每7天检测小鼠的体重和皮肤水分,在灌胃后第35天测试瘙痒行为和眼睑异常情况,同时记录存活率。在处死小鼠后评估单位面积毛发重量、胡须长度和炎症细胞情况。与对照组相比,用吉非替尼治疗的C57BL/6动物在存活率、单位面积毛发重量、皮肤水分变化、皮肤干燥、瘙痒行为、胡须不规则生长、眼睑异常和炎症细胞方面存在显著差异;用吉非替尼治疗的FVB/N动物仅在存活率、胡须不规则生长和眼睑异常方面与对照组存在显著差异。在本研究中,我们比较了C57BL/6和FVB/N小鼠中吉非替尼诱导的SAR的异同,这表明不同患者在临床上可能表现出不同症状,并为研究EGFR-TKIs诱导SAR的机制提供了实验依据。