Irsogladine maleate, a gastric mucosal protectant, suppresses intestinal polyp development in Apc-mutant mice.
Irsogladine maleate, a gastric mucosal protectant, suppresses intestinal polyp development in Apc-mutant mice.
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Irsogladine Maleate是一种胃粘膜保护剂，可抑制APC突变小鼠的肠道息肉发育。
DOI：
10.18632/oncotarget.7082
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发表时间：
2016-02-23
期刊：
影响因子：
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通讯作者：
Mutoh M
中科院分区：
文献类型：
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作者：
Onuma W;Tomono S;Miyamoto S;Fujii G;Hamoya T;Fujimoto K;Miyoshi N;Fukai F;Wakabayashi K;Mutoh M
本研究的目的是确定胃粘膜保护剂，抑制肠道肿瘤发生的小鼠模型。我们选择了六种胃粘膜保护剂（依卡贝特钠水合物、马来酸伊索拉定、瑞巴派特、索法酮、替普瑞酮和曲昔派特），并使用荧光素酶报告基因测定法检测它们对Caco-2细胞中氧化应激相关转录因子（包括AP-1、NF-jB、NRF 2、p53和STAT 3）活性的影响。在6种保护剂中，马来酸伊索拉定明显抑制NF-jB和AP-1的转录活性。此外，在家族性腺瘤性息肉病Min小鼠模型中检查了马来酸伊索拉定的化学预防特性。用5和50 ppm剂量的马来酸伊索拉定治疗可显著减少肠息肉的数量，分别为未治疗对照值的69%和66%。在这些息肉中，NF-jB下游靶标（如IL-1β和IL-6）的mRNA水平通过马来酸伊索拉定治疗而降低。此外，给予马来酸伊索拉定后，Min小鼠肝脏中氧化应激相关标志物（活性羰基物质）的水平明显降低。本研究表明，马来酸伊索拉定部分通过NF-jB信号通路抑制Min小鼠的肠息肉形成，从而降低氧化应激。
This study aimed to identify gastric mucosal protectants that suppress intestinal tumorigenesis in a mouse model. We chose six gastric mucosal protectants (ecabet sodium hydrate, irsogladine maleate, rebamipide, sofalcone, teprenone and troxipide) and examined their effects on the activity of oxidative stress-related transcriptional factors, including AP-1, NF-jB, NRF2, p53 and STAT3, in Caco-2 cells using a luciferase reporter gene assay. Among the six protectants, irsogladine maleate clearly inhibited NF-jB and AP-1 transcriptional activity. Furthermore, the chemopreventive property of irsogladine maleate was examined in a Min mouse model of familial adenomatous polyposis. Treatment with irsogladine maleate at doses of 5 and 50 ppm significantly reduced the number of intestinal polyps to 69% and 66% of the untreated control value, respectively. In these polyps, mRNA levels of the downstream targets of NF-jB, such as IL-1β and IL-6, were decreased by irsogladine maleate treatment. Moreover, the levels of oxidative stress-related markers, reactive carbonyl species, in the livers of Min mice were clearly decreased following the administration of irsogladine maleate. This study demonstrated that irsogladine maleate suppresses intestinal polyp formation in Min mice partly through the NF-jB signaling pathway, thus reducing oxidative stress.