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新型联合用药通过调节骨形态发生蛋白信号通路对结直肠癌发展的抑制作用:以及在研究中。

The inhibitory effects of the novel cocktail on colorectal cancer development through modulating BMP signaling pathway: and in study.

作者信息

Sepehr Amin, Aghamohammad Shadi, Ghanavati Roya, Bavandpour Ali Karimi, Talebi Malihe, Rohani Mahdi, Pourshafie Mohammad Reza

机构信息

Department of Bacteriology, Pasteur Institute of Iran, Tehran, Iran.

Behbahan Faculty of Medical Sciences, Behbahan, Iran.

出版信息

Heliyon. 2024 Aug 19;10(17):e36554. doi: 10.1016/j.heliyon.2024.e36554. eCollection 2024 Sep 15.

Abstract

This study investigates the impact of a five-strain cocktail (comprising two strains of , and one strain each of , , and ) on colorectal cancer (CRC) modulation by targeting the bone morphogenetic proteins (BMP) signaling pathway. Both and (models were employed. The antiproliferative effects of the cocktail on HT-29 cells were assessed via the MTT assay. Mice were divided into three groups: a negative control (treated with PBS), a positive control (treated with azoxymethane (AOM)/dextran sulfate sodium (DSS) + PBS), and a test group (treated with AOM/DSS +  cocktail in PBS). The role of the cocktail in inhibiting the BMP signaling pathway was evaluated using qRT-PCR for gene expression analysis and western blotting for β-catenin protein assessment in both models. The MTT assay results demonstrated a significant, time-dependent reduction in HT-29 cell proliferation. qRT-PCR indicated downregulation of the BMP signaling pathway in treated cells, which subsequently led to decreased expression of the hes1 gene, crucial for cell differentiation and proliferation control. This inhibitory effect was corroborated in the mice model, showing significant downregulation of BMP pathway genes and in the AOM/DSS/ cocktail-treated group. Additionally, western blotting revealed a marked decrease in β-catenin expression in both and experiments. Collectively, these findings suggest that the cocktail may aid in CRC prevention by downregulating the BMP signaling pathway.

摘要

本研究通过靶向骨形态发生蛋白(BMP)信号通路,调查了一种五菌株组合(包含两株 ,以及各一株 、 和 )对结直肠癌(CRC)调节的影响。采用了 和 两种模型。通过MTT试验评估该五菌株组合对HT-29细胞的抗增殖作用。将小鼠分为三组:阴性对照组(用PBS处理)、阳性对照组(用氧化偶氮甲烷(AOM)/葡聚糖硫酸钠(DSS)+PBS处理)和试验组(用AOM/DSS+五菌株组合的PBS溶液处理)。在两种模型中,使用qRT-PCR进行基因表达分析以及使用蛋白质印迹法评估β-连环蛋白,以评价该五菌株组合在抑制BMP信号通路中的作用。MTT试验结果表明,HT-29细胞增殖呈显著的时间依赖性降低。qRT-PCR表明处理后的细胞中BMP信号通路下调,这随后导致对细胞分化和增殖控制至关重要的hes1基因表达降低。在小鼠模型中也证实了这种抑制作用,在AOM/DSS/五菌株组合处理组中,BMP通路基因和 显著下调。此外,蛋白质印迹法显示在 和 实验中β-连环蛋白表达均显著降低。总的来说,这些发现表明该五菌株组合可能通过下调BMP信号通路有助于预防结直肠癌。

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