Department of Bacteriology, Pasteur Institute of Iran, Tehran, Iran.
Behbahan Faculty of Medical Sciences, Behbahan, Iran.
Iran Biomed J. 2024 Jul 1;28(4):168-78. doi: 10.61186/ibj.4012.
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.
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).
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.
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.
结直肠癌（CRC）患者的结肠微生物组成发生显著变化。本研究旨在评估乳酸菌混合物通过影响转化生长因子β（TGF-β）信号通路，在体外（HT-29 癌细胞）和体内（BALB/c 小鼠）模型中对 CRC 的调节作用。
本研究采用 MTT 法评估了一种天然潜在益生菌乳酸菌混合物对 HT-29 癌细胞的增殖抑制作用。还通过 qRT-PCR 评估了与 TGF-β信号通路相关的基因的 RNA 表达水平，该通路在三个水平上进行：受体、调节和抑制 SMAD。最后，通过三组小鼠进行体内试验：一组为对照组（PBS），一组为疾病组（氧化偶氮甲烷[AOM]/葡聚糖硫酸钠[DSS]+PBS），一组为治疗组（AOM/DSS+PBS 中的乳酸菌混合物）。
MTT 结果显示，HT-29 癌细胞经 120 h 处理后增殖明显下降。此外，qRT-PCR 显示 HT-29 处理细胞中 smad2/3 基因表达下调，smad4 基因表达水平降低。此外，在小鼠模型中，AOM/DSS/Lactobacillus 治疗组 tgf-βR1 基因下调，但 AOM/DSS 组无此现象。体内模型也观察到 smad4 基因表达下调。
研究结果表明，我们的新型益生菌乳酸菌混合物可能通过下调 TGF-β信号通路对抑制 CRC 进展产生积极影响。
