The contribution of keratinocytes in capecitabine-stimulated hand-foot-syndrome
The contribution of keratinocytes in capecitabine-stimulated hand-foot-syndrome
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角质形成细胞在卡培他滨刺激的手足综合征中的作用
DOI：
10.1016/j.etap.2016.12.001
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发表时间：
2017-01-01
影响因子：
4.3
通讯作者：
He, Qiaojun
中科院分区：
文献类型：
--
作者：
Chen, Min;Chen, Jian;He, Qiaojun
卡培他滨作为多种肿瘤类型的一线治疗药物，其严重的手足综合征（HFS）缺点限制了其临床应用。然而，卡培他滨诱导的HFS的病理生理和机制尚不清楚。我们首先建立了卡培他滨诱导HFS的实验小鼠模型，结果显示，6只小鼠中有3只在第5天出现HFS，有5只在第30天出现HFS。卡培他滨诱导的HFS在体内减少了角质层。此外，我们发现卡培他滨可以通过激活凋亡途径和降低线粒体膜电位显著诱导体外角质形成细胞死亡。综上所述，这些结果表明卡培他滨的HFS可能是在激活caspase依赖的凋亡途径后，通过刺激细胞内线粒体功能障碍减少角质层而发展起来的。(C) 2016 Elsevier B.V.版权所有
Capecitabine, as the first-line treatment for multiple tumor types, has a serious drawback of hand-foot-syndrome (HFS) that limits its clinical use. However, the pathophysiology and mechanism of capecitabine-induced HFS is rarely known. Here we built the experimental mouse model of HFS induced by capecitabine at first and it was shown that 3 of 6 mice appeared HFS in the 5th day and 5 mice occurred HFS in the 30th day. The corneous layer was reduced in capecitabine-induced HFS in vivo. Moreover, we found that capecitabine could significantly induce keratinocytes cells death in vitro through activated apoptosis pathway and decreased mitochondrial membrane potential. In conclusion, these results suggested that HFS of capecitabine may be developed from reduction of corneous layer through stimulation of intracellular mitochondrial dysfunction following activation of caspase-dependent apoptosis pathway. (C) 2016 Elsevier B.V. All rights reserved.