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口服微囊化 BAA-999 和番茄红素可调节结直肠鼠模型中 IGF-1/IGF-1R/IGFBP3 蛋白的表达。

Oral Administration of Microencapsulated BAA-999 and Lycopene Modulates IGF-1/IGF-1R/IGFBP3 Protein Expressions in a Colorectal Murine Model.

机构信息

Graduate Studies in Food Science, School of Chemistry, Autonomous University of Queretaro, Cerro de las Campanas S/N, C.P. 76010, Querétaro, Mexico.

Chemical Engineering Department, National Technological of Mexico, Tecnológico y Antonio García Cubas S/N C.P. 38010, Guanajuato, Mexico.

出版信息

Int J Mol Sci. 2019 Aug 31;20(17):4275. doi: 10.3390/ijms20174275.

Abstract

The Insulin-like growth factor-I/Insulin-like growth factor-I receptor (IGF-1/IGF-1R) system is a major determinant in colorectal cancer (CRC) pathogenesis. Probiotics (, BF) and lycopene (LYC) have been individually researched for their beneficial effects in the prevention of CRC. However, the effect of a combined treatment of microencapsulated BF and LYC on IGF-1/IGF-1R/IGFBPs (Insulin-like growth factor-binding proteins) expression in an azoxymethane (AOM)-dextran sulfate sodium (DSS)-induced CRC model have not been demonstrated. BF was microencapsulated by the spray drying technique, with high viability, and daily gavaged with LYC for 16 weeks to CD-1 mice in an AOM-DSS model. The results indicated that BF- and BF + LYC-treated groups had significantly lower inflammation grade, tumor incidence (13-38%) and adenocarcinoma (13-14%) incidence compared to the AOM + DSS group (80%), whereas LYC treatment only protected against inflammation grade and incidence. Caecal, colonic and fecal pH and β-glucuronidase (β-GA) values were significantly normalized by BF and LYC. Similarly, BF and BF + LYC treatments significantly reduced both the positive rate and expression grade of IGF-1 and IGF-1R proteins and normalized Insulin-like growth factor-binding protein-3 (IGFBP3) expression. Based on intestinal parameters related to the specific colon carcinogenesis in an AOM-DSS-induced model, LYC and microencapsulated BF supplementation resulted in a significant chemopreventive potential through the modulation of IGF-1/IGF-1R system.

摘要

胰岛素样生长因子-I/胰岛素样生长因子-I 受体 (IGF-1/IGF-1R) 系统是结直肠癌 (CRC) 发病机制的主要决定因素。益生菌 (BF) 和番茄红素 (LYC) 已分别研究其在预防 CRC 中的有益作用。然而,微囊化 BF 和 LYC 联合治疗对氧化偶氮甲烷 (AOM)-葡聚糖硫酸钠 (DSS) 诱导的 CRC 模型中 IGF-1/IGF-1R/IGFBPs(胰岛素样生长因子结合蛋白)表达的影响尚未得到证实。采用喷雾干燥技术对 BF 进行微囊化,具有高存活率,并在 AOM-DSS 模型中用 LYC 每日灌胃 16 周。结果表明,与 AOM+DSS 组(80%)相比,BF 和 BF+LYC 治疗组的炎症程度、肿瘤发生率(13%-38%)和腺癌发生率(13%-14%)明显降低,而 LYC 治疗仅能预防炎症程度和发生率。盲肠、结肠和粪便 pH 值和β-葡萄糖醛酸酶(β-GA)值均通过 BF 和 LYC 得到显著正常化。同样,BF 和 BF+LYC 治疗可显著降低 IGF-1 和 IGF-1R 蛋白的阳性率和表达水平,并使胰岛素样生长因子结合蛋白-3(IGFBP3)表达正常化。基于 AOM-DSS 诱导模型中与特定结肠癌变相关的肠道参数,LYC 和微囊化 BF 补充通过调节 IGF-1/IGF-1R 系统表现出显著的化学预防潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2952/6747182/7d72430aeb4b/ijms-20-04275-g001.jpg

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