Role of Native Probiotic Lactobacillus Species via TGF-β Signaling Pathway Modulation in CRC

Q2 Biochemistry, Genetics and Molecular Biology
Amin Sepehr, Shadi Aghamohammad, Roya Ghanavati, Malihe Talebi, Mohammad Reza Pourshafie, Mahdi Rohani
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引用次数: 0

Abstract

Background: Colon microbiome composition in colorectal cancer (CRC) patients undergoes remarkable changes. The present study was designed to assess the impact of Lactobacillus mixture on the regulating the CRC by influencing the transforming growth factor beta (TGF-β) signaling pathway in both in vitro (HT-29 cancer cells) and in vivo (BALB/c mice) models.

Methods: In this study, the antiproliferative effect of a native potential probiotic Lactobacillus mixture on HT-29 cancer cells was evaluated using the MTT assay method. Also, qRT-PCR was performed to assess the RNA expression level of genes associated with the TGF-β signaling pathway at three levels: receptor, regulatory, and inhibitory SMADs. Finally, the in vivo assays were investigated by three groups of mice: a naive group (PBS), a disease group (azoxymethane [AOM]/ dextran sulfate sodium [DSS] + PBS), and a treatment group (AOM/DSS + Lactobacillus mixture in PBS).

Results: The MTT results showed a significant decrease in proliferation of HT-29 cancer cells after 120 h of treatment. Furthermore, qRT-PCR demonstrated the downregulation of the smad2/3 gene expression in HT-29-treated cells and also reduction in the level of smad4 gene expression. In addition, in the mouse model, the tgf-βR1 gene was downregulated in the group treated with AOM/DSS/Lactobacillus, but not the AOM/DSS group. A downregulation of smad4 gene expression was also observed in in vivo models.

Conclusion: The obtained results suggest that our novel probiotic Lactobacillus mixture could have a positive impact on the inhibition of the CRC progression by downregulating the TGF-β signaling pathway.

本地益生菌乳酸杆菌通过 TGF-β 信号通路调节在癌症癌症中的作用
背景:结肠直肠癌(CRC)患者的结肠微生物组组成发生了显著变化。本研究旨在评估乳酸菌混合物在体外(HT-29 癌细胞)和体内(BALB/c 小鼠)模型中通过影响转化生长因子 beta(TGF-β)信号通路对调节 CRC 的影响:本研究采用 MTT 检测法评估了一种本地潜在益生菌乳酸杆菌混合物对 HT-29 癌细胞的抗增殖作用。此外,还采用 qRT-PCR 方法评估了与 TGF-β 信号通路相关的基因在受体、调节和抑制 SMADs 三个水平上的 RNA 表达水平。最后,对三组小鼠进行了体内试验:天真组(PBS)、疾病组(偶氮甲烷[AOM]/右旋糖酐硫酸钠[DSS]+PBS)和治疗组(AOM/DSS+PBS中的乳酸杆菌混合物):MTT结果表明,治疗120小时后,HT-29癌细胞的增殖明显减少。此外,qRT-PCR 显示,HT-29 处理细胞中的 smad2/3 基因表达下调,smad4 基因表达水平也有所下降。此外,在小鼠模型中,AOM/DSS/乳酸杆菌组的tgf-βR1基因下调,而AOM/DSS组没有下调。在体内模型中也观察到了smad4基因表达的下调:结果表明,我们的新型益生菌乳酸菌混合物可通过下调 TGF-β 信号通路对抑制 CRC 的进展产生积极影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Iranian Biomedical Journal
Iranian Biomedical Journal Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)
CiteScore
3.20
自引率
0.00%
发文量
42
审稿时长
8 weeks
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