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嗜酸乳杆菌混合物对 HT-29 结肠癌细胞生长的抑制作用及对 Notch 和 Wnt/β-连环蛋白信号通路的调节作用。

Inhibitory effects of Lactobacilli cocktail on HT-29 colon carcinoma cells growth and modulation of the Notch and Wnt/β-catenin signaling pathways.

机构信息

Microbial Biotechnology Research Center, Iran University of Medical Sciences, Tehran, Iran; Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran; Microbiology Department, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran.

出版信息

Microb Pathog. 2020 Feb;139:103829. doi: 10.1016/j.micpath.2019.103829. Epub 2019 Nov 2.

DOI:10.1016/j.micpath.2019.103829
PMID:31682995
Abstract

Probiotics could be considered as attractive candidates for preventing tumor growth through maintaining homeostasis. The aim of this study was to evaluate the inhibitory effect of a cocktail of five Lactobacillus species on human colorectal carcinoma cell line HT-29. The anti-proliferative and apoptotic effects of Lactobacilli cocktail were evaluated using MTT and flow cytometry tests, respectively. Quantitative real-time polymerase chain reaction (qPCR) was used to analyze the expression of several genes in the Notch (notch, hes1, msi1, and numb) and Wnt/β-catenin (CTNNB1 and CCND1) pathways, following the treatment of HT-29 cells with Lactobacilli cocktail. The treatment by Lactobacilli cocktail induced a significant anti-proliferative effect and late stage apoptosis among the cancer cells (p < 0.05). Compared to the untreated cells, Lactobacilli cocktail induced the down-regulation of notch, hes1, and msi1 genes and up-regulation of numb gene in the Notch pathway as well as the down-regulation of CTNNB1 and CCND1 genes in the Wnt/β-catenin pathway in a time-dependent manner (p < 0.05). CONCLUSION: Lactobacilli cocktail was shown to have beneficial anti-tumor effects on HT-29 cells by modulating the Notch and Wnt/β-catenin pathways; therefore, the use of Lactobacilli probiotics as nutritional supplements may prevent the incidence of colon cancer.

摘要

益生菌可以被认为是通过维持体内平衡来预防肿瘤生长的有吸引力的候选物。本研究的目的是评估五种乳杆菌属混合物对人结直肠癌细胞系 HT-29 的抑制作用。使用 MTT 和流式细胞术分别评估乳杆菌混合物的抗增殖和促凋亡作用。用定量实时聚合酶链反应(qPCR)分析 Notch(notch、hes1、msi1 和 numb)和 Wnt/β-catenin(CTNNB1 和 CCND1)途径中几个基因的表达,用乳杆菌混合物处理 HT-29 细胞后。乳杆菌混合物的处理在癌细胞中诱导了显著的抗增殖作用和晚期凋亡(p<0.05)。与未经处理的细胞相比,乳杆菌混合物在时间依赖性方式下诱导 Notch 途径中 notch、hes1 和 msi1 基因的下调和 numb 基因的上调以及 Wnt/β-catenin 途径中 CTNNB1 和 CCND1 基因的下调(p<0.05)。结论:乳杆菌混合物通过调节 Notch 和 Wnt/β-catenin 途径对 HT-29 细胞显示出有益的抗肿瘤作用;因此,使用乳杆菌益生菌作为营养补充剂可能预防结肠癌的发生。

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