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马齿苋提取物通过抑制 Wnt/β-连环蛋白信号通路减少肠道微生物失衡并抑制结直肠癌进展。

Portulaca oleracea extract reduces gut microbiota imbalance and inhibits colorectal cancer progression via inactivation of the Wnt/β-catenin signaling pathway.

机构信息

Department of General Surgery, the Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, PR China.

Department of General Surgery, the Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, PR China.

出版信息

Phytomedicine. 2022 Oct;105:154279. doi: 10.1016/j.phymed.2022.154279. Epub 2022 Jun 16.

DOI:10.1016/j.phymed.2022.154279
PMID:35963192
Abstract

BACKGROUND

Portulaca oleracea is a known medicinal plant with antioxidant, anti-inflammatory, and anticancer activities, and it may also function an important role in colorectal cancer (CRC).

PURPOSE

We probed into study the critical function of Portulaca oleracea extract (POE) in CRC and the related downstream factors.

METHODS

Azoxymethane (AOM) and dextransodiumsulfate (DSS) were used to induce mouse models of CRC, which were then administered different doses of POE to evaluate the therapeutic effects of POE on CRC. Diversity, abundance, and function of gut microbiota were analyzed. Moreover, the potential molecular targets of POE inhibiting CRC development were determined. Expression of c-Myc and cyclin D1 as well as CRC cell proliferation and apoptosis was detected.

RESULTS

POE treatment inhibited AOM/DSS-induced CRC development in mice and ameliorated gut microbial imbalance. Bioinformatic analysis revealed marked differences in the gut microbiota between CRC samples and normal samples and that 20 differential microbiota may be involved in CRC development through the Wnt signaling pathway. Additionally, c-Myc and cyclin D1 were identified to be the key downstream target genes of the Wnt/β-catenin signaling pathway. In vitro data revealed that POE played a suppressive role in the proliferation of CRC cells by reducing the expression of c-Myc and cyclin D1 and inactivating the Wnt/β-catenin signaling pathway.

CONCLUSION

This study underlines that POE reduces gut microbiota imbalance and inhibits CRC development and progression via inactivation of the Wnt/β-catenin signaling pathway and downregulation of c-Myc and cyclin D1 expression, which is expected to be a potential biomarker for CRC.

摘要

背景

马齿苋是一种已知的药用植物,具有抗氧化、抗炎和抗癌活性,它在结直肠癌(CRC)中可能也具有重要作用。

目的

我们探究马齿苋提取物(POE)在 CRC 中的关键作用及其相关下游因素。

方法

采用氧化偶氮甲烷(AOM)和葡聚糖硫酸钠(DSS)诱导小鼠 CRC 模型,然后给予不同剂量的 POE 评估 POE 对 CRC 的治疗作用。分析肠道微生物群落的多样性、丰度和功能。此外,还确定了 POE 抑制 CRC 发展的潜在分子靶标。检测 c-Myc 和 cyclin D1 的表达以及 CRC 细胞的增殖和凋亡。

结果

POE 治疗抑制了 AOM/DSS 诱导的小鼠 CRC 发生,并改善了肠道微生物失衡。生物信息学分析显示,CRC 样本和正常样本之间的肠道微生物存在明显差异,通过 Wnt 信号通路,20 种差异微生物可能参与 CRC 的发生。此外,c-Myc 和 cyclin D1 被鉴定为 Wnt/β-catenin 信号通路的关键下游靶基因。体外数据显示,POE 通过降低 c-Myc 和 cyclin D1 的表达和失活 Wnt/β-catenin 信号通路,在 CRC 细胞的增殖中发挥抑制作用。

结论

本研究强调 POE 通过失活 Wnt/β-catenin 信号通路和下调 c-Myc 和 cyclin D1 的表达,减少肠道微生物失衡,抑制 CRC 的发生和发展,有望成为 CRC 的潜在生物标志物。

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