CXCL9 attenuated chemotherapy-induced intestinal mucositis by inhibiting proliferation and reducing apoptosis
CXCL9 attenuated chemotherapy-induced intestinal mucositis by inhibiting proliferation and reducing apoptosis
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DOI：
10.1016/j.biopha.2011.03.008
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发表时间：
2011-12-01
影响因子：
7.5
通讯作者：
Wang, Yu
中科院分区：
文献类型：
--
作者：
Han, Xiaodong;Wu, Zhenqian;Wang, Yu
癌症化疗引起的粘膜炎是一种常见的问题，目前还没有明确的治疗方法。5-氟尿嘧啶(5-FU)是一种治疗实体瘤的常用细胞毒剂。全球基因表达阵列被用来识别与粘膜炎发病机制有关的遗传信号。趋化因子(C-X-C基序)配体9(CXCL9)是已鉴定的具有特征性基因表达谱的候选基因之一，其时间表达模式与5-FU化疗后小肠的损伤和再生阶段相关。我们发现预防性给予CXCL9能够减轻化疗引起的粘膜炎、体重减轻和腹泻的严重程度。CXCL9还提高了小鼠对致命剂量化疗的耐受性。此外，我们还证实了CXCL9能够通过抑制化疗前正常肠粘膜细胞的增殖和减少5-FU诱导的肠隐窝细胞的凋亡来促进肠细胞的增殖和再生。因此，CXCL9预处理是临床上缓解化疗引起的肠粘膜炎的一种新的有前景的策略。(C)2011年爱思唯尔·马森公司。版权所有。
Mucositis arising from cancer chemotherapy is a common problem for which there is no definitive treatment. 5-fluorouracil (5-FU) is a common cytotoxic agent used to treat solid tumors. A global gene expression array was performed to identify genetic signals involved in the pathogenesis of mucositis. The chemokine (C-X-C motif) ligand 9 (CXCL9) was one of the candidates identified that presented a characteristic gene expression profile; its temporal expression pattern was correlated with the damage and regeneration phases of the small intestine upon 5-FU chemotherapy. We found that prophylactic CXCL9 administration was able to attenuate the severity of mucositis, weight loss and diarrhea caused by chemotherapy. CXCL9 also increased the tolerance of the mice to lethal-dose chemotherapy. Moreover, we demonstrated that CXCL9 was able to promote the proliferation and regeneration of intestinal cells by inhibiting the proliferation of normal intestinal mucosal cells prior to chemotherapy and by reducing the 5-FU-induced apoptosis in intestinal crypts. Thus, pretreatment with CXCL9 is a new and promising strategy for the alleviation of chemotherapy-induced intestinal mucositis in clinical settings. (C) 2011 Elsevier Masson SAS. All rights reserved.