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传统维吾尔药栎瘿水提物诱导结直肠癌细胞凋亡和自噬性细胞死亡。

Traditional Uyghur medicine Quercus infectoria galls water extract triggers apoptosis and autophagic cell death in colorectal cancer cells.

机构信息

Department of Biological Medicines & Shanghai Engineering Research Center of Immunotherapeutics, School of Pharmacy, Fudan University, Shanghai, 201203, China.

Pudong New Area People's Hospital Affiliated to Shanghai University of Medicine and Health Sciences, Shanghai, 201200, China.

出版信息

BMC Complement Med Ther. 2020 Dec 3;20(1):371. doi: 10.1186/s12906-020-03167-0.

Abstract

BACKGROUND

The water extract of Quercuse infectoria galls (QIG) is the active ingredient of Uyghur medicine Xipayi Kui Jie'an (KJA) which has promising therapeutic effects on Ulcerative Colitis (UC) as an alternative medicine. Considering the relationship between UC and the development of colorectal cancer (CRC), the present work aims to explore the direct anti-CRC activity of QIG extract.

METHODS

CCK8 assay and flow cytometry were used to detect cytotoxicity and apoptosis. Transmission electron microscopy (TEM), flow cytometry, laser confocal and western blotting were performed to examine autophagy. We also adopted Reactive Oxygen Assay kit, as well as transwell and wound healing tests to study the underlying mechanism of QIG against CRC cells.

RESULTS

First, we found that QIG extract could suppress the viability of CRC cells and trigger caspases-dependent apoptosis. Subsequently, we proved for the first time that QIG extract also triggered autophagic cell death in CRC cells, which together with apoptosis contributed to the cytotoxic effect on CRC cells. Further investigation revealed that QIG-induced cytotoxicity associated with intracellular ROS accumulation which could suppress the AKT/mTOR signaling pathway, and then induce autophagy and inhibit cell growth. Besides, Erk signaling pathway was also involved in the process of autophagic cell death. Moreover, QIG extract also influenced EMT process and inhibited CRC cell migration.

CONCLUSION

Altogether, this study provides a basis for the utilization of QIG as an alternative medicine for CRC prevention and treatment.

摘要

背景

五倍子水提物是维吾尔药西帕依溃结安的有效成分,对溃疡性结肠炎有较好的疗效。鉴于溃疡性结肠炎与结直肠癌的发展关系,本工作旨在探索五倍子水提物对结直肠癌细胞的直接抗癌活性。

方法

采用 CCK8 法和流式细胞术检测细胞毒性和细胞凋亡。透射电镜、流式细胞术、激光共聚焦和 Western blot 检测自噬。还采用活性氧测定试剂盒、transwell 和划痕愈合试验研究五倍子水提物对 CRC 细胞的作用机制。

结果

首先,我们发现五倍子水提物可抑制 CRC 细胞的活力并触发 caspase 依赖性细胞凋亡。随后,我们首次证明五倍子水提物也可诱导 CRC 细胞发生自噬性细胞死亡,这与细胞凋亡共同导致对 CRC 细胞的细胞毒性作用。进一步研究表明,五倍子诱导的细胞毒性与细胞内 ROS 积累有关,可抑制 AKT/mTOR 信号通路,进而诱导自噬并抑制细胞生长。此外,Erk 信号通路也参与了自噬性细胞死亡过程。此外,五倍子水提物还影响 EMT 过程并抑制 CRC 细胞迁移。

结论

总之,本研究为五倍子作为结直肠癌预防和治疗的替代药物提供了依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4376/7712637/11264bcdd22b/12906_2020_3167_Fig1_HTML.jpg

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