Curcumin Inhibits 5-Fluorouracil-induced Up-regulation of CXCL1 and CXCL2 of the Colon Associated with Attenuation of Diarrhoea Development
Curcumin Inhibits 5-Fluorouracil-induced Up-regulation of CXCL1 and CXCL2 of the Colon Associated with Attenuation of Diarrhoea Development
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DOI：
10.1111/bcpt.12619
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发表时间：
2016-12-01
影响因子：
3.1
通讯作者：
Narita, Minoru
中科院分区：
文献类型：
--
作者：
Sakai, Hiroyasu;Kai, Yuki;Narita, Minoru
化合物5-氟尿嘧啶（5-FU）用于癌症化疗，已知会引起腹泻。我们最近报道，趋化因子（C-X-C基序）配体1（CXCL 1）和中性粒细胞在结肠粘膜显着增加，由5-FU的管理在小鼠。姜黄素具有抗炎、抗肿瘤和抗氧化特性。因此，我们研究了姜黄素对5-FU诱导的腹泻发展和结肠中CXCL 1和CXCL 2上调的影响。小鼠给予5-FU（50 mg/kg，腹腔注射）每日一次，共4天。姜黄素（100或300 mg/kg，p.o.）在5-FU首次给药前一天给药，并在5-FU给药前30分钟给药。实时定量RT-PCR检测结肠组织中CXCL 1和CXCL 2的基因表达水平。姜黄素减少5-FU诱导的腹泻发展。在此条件下，CXCL 1和CXCL 2基因上调5-FU给药抑制姜黄素。5-FU在体外也能促进CXCL 1和CXCL 2的基因表达。姜黄素、Bay-117082和硼替佐米（NF-B抑制剂）、C646（p300/环磷酸腺苷反应元件结合蛋白-组蛋白乙酰转移酶（HAT）抑制剂）可抑制5-FU诱导的CXCL 1和CXCL 2基因表达上调。总之，这些发现表明姜黄素通过抑制NF-B和HAT活化来预防腹泻的发展。
The compound 5-fluorouracil (5-FU) is used in cancer chemotherapy and is known to cause diarrhoea. We recently reported that chemokine (C-X-C motif) ligand 1 (CXCL1) and neutrophils in the colonic mucosa were markedly increased by the administration of 5-FU in mice. Curcumin has anti-inflammatory, antitumour and antioxidant properties. Therefore, we examined the effect of curcumin on 5-FU-induced diarrhoea development and CXCL1 and CXCL2 up-regulation in the colon. Mice were given 5-FU (50 mg/kg, i.p.) daily for 4 days. Curcumin (100 or 300 mg/kg, p.o.) was administered on the day before the first administration of 5-FU and administered 30 min. before the administration of 5-FU. Gene expression levels of CXCL1 and CXCL2 in the colon were examined by real-time RT-PCR. Curcumin reduced the 5-FU-induced diarrhoea development. Under this condition, the CXCL1 and CXCL2 gene up-regulated by 5-FU administration was inhibited by curcumin. The gene expression of CXCL1 and CXCL2 was also enhanced by 5-FU application in vitro. The 5-FU-induced up-regulated CXCL1 and CXCL2 gene expressions were inhibited by curcumin, Bay-117082 and bortezomib, nuclear factor kappa B (NF-B) inhibitors, C646, a p300/cyclic adenosine monophosphate response element-binding protein-histone acetyltransferase (HAT) inhibitor. In conclusion, these findings suggested that curcumin prevented the development of diarrhoea by inhibiting NF-B and HAT activation.