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香草醛衍生物通过E-钙黏蛋白/β-连环蛋白通路逆转诱导的结直肠癌增殖和迁移。

Vanillin Derivatives Reverse -Induced Proliferation and Migration of Colorectal Cancer Through E-Cadherin/β-Catenin Pathway.

作者信息

Zhou Zhongkun, Wang Yiqing, Ji Rui, Zhang Dekui, Ma Chi, Ma Wantong, Ma Yunhao, Jiang Xinrong, Du Kangjia, Zhang Rentao, Chen Peng

机构信息

School of Pharmacy, Lanzhou University, Lanzhou, China.

The First Hospital of Lanzhou University, Lanzhou, China.

出版信息

Front Pharmacol. 2022 Mar 4;13:841918. doi: 10.3389/fphar.2022.841918. eCollection 2022.

Abstract

Colorectal cancer (CRC) is a common clinical malignant tumor and closely related to intestinal microbiome disorders. Especially, () is one of the most prevalent pathogens in CRC. However, its change in CRC patients of Northwest China, an area with a high incidence of gastrointestinal tumors, is unclear, and therapeutic strategies targeting remain unresolved. Here, fecal samples of healthy people and CRC patients were studied using 16S rRNA sequencing to explore microbial community alterations. Additionally, vanillin derivate (IPM711 and IPM712) intervention by coculture with CRC cells and potential mechanism were investigated. Results showed that intestinal microbial homeostasis was gradually dysregulated, and the abundance of was higher in CRC patients. Moreover, IPM711 and IPM712 showed better anti- activity than vanillin by increasing cell membrane permeability and destroying bacterial integrity. In addition, IPM711 and IPM712 could downregulate the expression of E-cadherin and β-catenin, thus, suppressing the migration of HCT116. Collectively, IPM711 and IPM712 have both anticolorectal cancer and anti- activities, providing potential natural product drug candidates for microbe-targeted strategies for the treatment of CRC.

摘要

结直肠癌(CRC)是一种常见的临床恶性肿瘤,与肠道微生物群紊乱密切相关。特别是,(某病原体,原文此处未给出具体名称)是CRC中最普遍的病原体之一。然而,在中国西北这个胃肠道肿瘤高发地区,CRC患者体内该病原体的变化尚不清楚,针对该病原体的治疗策略也尚未解决。在此,通过16S rRNA测序研究健康人和CRC患者的粪便样本,以探索微生物群落的变化。此外,还研究了香草醛衍生物(IPM711和IPM712)与CRC细胞共培养的干预作用及其潜在机制。结果表明,肠道微生物稳态逐渐失调,CRC患者体内该病原体的丰度更高。此外,IPM711和IPM712通过增加细胞膜通透性和破坏细菌完整性,显示出比香草醛更好的抗(该病原体,原文此处未给出具体名称)活性。此外,IPM711和IPM712可下调E-钙黏蛋白和β-连环蛋白的表达,从而抑制HCT116细胞的迁移。总体而言,IPM711和IPM712具有抗结直肠癌和抗(该病原体,原文此处未给出具体名称)的活性,为针对微生物的结直肠癌治疗策略提供了潜在的天然产物候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ce20/8931468/309abaf816cc/fphar-13-841918-g001.jpg

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