摘要
背景:最近的流行病学和实验研究表明,肥胖是结直肠癌(CRC)的主要危险因素。经常摄入高脂肪饮食可促进肥胖ND代谢综合征通过增加胰岛素抵抗和炎症反应,促进癌变。在此之前,我们已经证明了对多元醇途径酶醛糖还原的抑制作用。TASE(AR)可防止致癌物和炎症生长因子引起的CRC。然而,AR抑制对高脂饮食(HFD)诱导的APC缺陷型Min(M)肠息肉形成的影响溃疡性肠瘤;ApcMin/)小鼠尚不清楚。 方法:我们观察了AR抑制剂,fiarestat对Hfd诱导的ApcMin/小鼠肠息肉形成的影响,这是一种很好的结肠癌模型。 结果:用APCMin/小鼠喂养12周的HFD可显著增加小肠和大肠息肉的形成,并且与HFD一起给药可防止O数的增加。f肠息肉。Fidarestat还减少了HFDD处理的APC Min小鼠肠道息肉的大小。此外,β-catenin,pna,pkc-β2,P-aKT,pp 65,cox-2,an的表达水平。hfd处理后小鼠小肠和大肠d iNOS明显升高,AR抑制剂抑制。 结论:我们的结果表明,由于APC基因突变,该药物可作为一种潜在的肠道肿瘤的化学预防药物。
关键词: 醛糖还原酶,纤溶酶,APC小鼠,高脂饮食,结肠癌,息肉。
Current Cancer Drug Targets
Title:Aldose Reductase Inhibitor, Fidarestat Prevents High-fat Diet-induced Intestinal Polyps in ApcMin/+ Mice
Volume: 18 Issue: 9
关键词: 醛糖还原酶,纤溶酶,APC小鼠,高脂饮食,结肠癌,息肉。
摘要: Background: Recent epidemiological and experimental studies have shown that obesity is a major risk factor for Colorectal Cancer (CRC). Regular intake of high fat-containing diet can promote obesity and metabolic syndrome by increasing the insulin resistance and inflammatory response which contribute to carcinogenesis. Previously, we have shown that inhibition of polyol pathway enzyme aldose reductase (AR) prevents carcinogens- and inflammatory growth factorsinduced CRC. However, the effect of AR inhibition on a high-fat diet (HFD)-induced formation of intestinal polyps in Apc-deficient Min (multiple intestinal neoplasia; ApcMin/+) mice is not known.
Methods: We examined the effect of AR inhibitor, fidarestat on the HFD-induced formation of preneoplastic intestinal polyps in ApcMin/+ mice which is an excellent model of colon cancer.
Results: APCMin/+ mice fed for 12 weeks of HFD caused a significant increase in the formation of polyps in the small and large intestines and fidarestat given along with the HFD prevented the number of intestinal polyps. Fidarestat also decreased the size of the polyps in the intestines of HFDtreated APC Min mice. Further, the expression levels of beta-catenin, PCNA, PKC-β2, P-AKT, Pp65, COX-2, and iNOS in the small and large intestines of HFD-treated mice significantly increased, and AR inhibitor prevented it.
Conclusion: Our results thus suggest that fidarestat could be used as a potential chemopreventive drug for intestinal cancers due to APC gene mutations.
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Cite this article as:
Aldose Reductase Inhibitor, Fidarestat Prevents High-fat Diet-induced Intestinal Polyps in ApcMin/+ Mice, Current Cancer Drug Targets 2018; 18 (9) . https://dx.doi.org/10.2174/1568009617666170808105633
DOI https://dx.doi.org/10.2174/1568009617666170808105633 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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