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C.A. 迈耶(Rg3)通过PI3K/AKT/miRNA-21途径抑制糖酵解改善Atp4a小鼠的胃癌前病变。

C.A. Meyer (Rg3) Ameliorates Gastric Precancerous Lesions in Atp4a Mice via Inhibition of Glycolysis through PI3K/AKT/miRNA-21 Pathway.

作者信息

Liu Wei, Pan Hua-Feng, Yang Liang-Jun, Zhao Zi-Ming, Yuan Dong-Sheng, Liu Yuan-Liang, Lin Li-Zhu

机构信息

Guangzhou University of Chinese Medicine, Guangzhou 510405, China.

First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510095, China.

出版信息

Evid Based Complement Alternat Med. 2020 Jan 31;2020:2672648. doi: 10.1155/2020/2672648. eCollection 2020.

DOI:10.1155/2020/2672648
PMID:32076440
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7019209/
Abstract

Gastric cancer, one of the most common types of cancers, develops over a series of consecutive histopathological stages. As such, the analysis and research of the gastric precancerous lesions (GPLs) play an important role in preventing the occurrence of gastric cancer. Ginsenoside Rg3 (Rg3), an herbal medicine, plays an important role in the prevention and treatment of various cancers. Studies have demonstrated a correlation between glycolysis and gastric cancer progression. Herein, the aim of the present study was to clarify the potential role for glycolysis pathogenesis in Rg3-treated GPL in Atp4a mice. The GPL mice model showed chronic gastritis, intestinal metaplasia, and more atypical hyperplasia in gastric mucosa. According to the results of HE and AB-PAS staining, it could be confirmed that GPL mice were obviously reversed by Rg3. Additionally, the increased protein levels of PI3K, AKT, mTOR, HIF-1, LDHA, and HK-II, which are crucial factors for evaluating GPL in the aspect of glycolysis pathogenesis in the model group, were downregulated by Rg3. Meanwhile, the miRNA-21 expression was decreased and upregulated by Rg3. Furthermore, the increased gene levels of Bcl-2 and caspase-3 were attenuated in Rg3-treated GPL mice. In conclusion, the findings of this study imply that abnormal glycolysis in GPL mice was relieved by Rg3 via regulation of the expressions of PI3K, AKT, mTOR, HIF-1, LDHA, HK-II, and miRNA-21. Rg3 is an effective supplement for GPL treatment and can be harnessed to inhibit proliferation and induce apoptosis of GPL cells.

摘要

胃癌是最常见的癌症类型之一,其发展经历一系列连续的组织病理学阶段。因此,对胃癌前病变(GPLs)的分析和研究在预防胃癌发生中起着重要作用。人参皂苷Rg3(Rg3)作为一种草药,在各种癌症的预防和治疗中发挥着重要作用。研究表明糖酵解与胃癌进展之间存在关联。在此,本研究的目的是阐明糖酵解发病机制在Rg3处理的Atp4a小鼠GPL中的潜在作用。GPL小鼠模型显示出慢性胃炎、肠化生以及胃黏膜中更多的非典型增生。根据苏木精-伊红(HE)和阿尔辛蓝-过碘酸雪夫(AB-PAS)染色结果,可以证实Rg3可明显逆转GPL小鼠的病变。此外,在模型组中,作为评估GPL糖酵解发病机制方面关键因素的PI3K、AKT、mTOR、HIF-1、LDHA和HK-II的蛋白水平升高,而Rg3可使其下调。同时,Rg3使miRNA-21表达降低后又上调。此外,在Rg3处理的GPL小鼠中,Bcl-2和caspase-3基因水平的升高得到缓解。总之,本研究结果表明,Rg3通过调节PI3K、AKT、mTOR、HIF-1、LDHA、HK-II和miRNA-21的表达,缓解了GPL小鼠的糖酵解异常。Rg3是治疗GPL的有效补充剂,可用于抑制GPL细胞的增殖并诱导其凋亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/471e/7019209/30677c0273f5/ECAM2020-2672648.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/471e/7019209/f1ab871daf0e/ECAM2020-2672648.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/471e/7019209/287a5659f671/ECAM2020-2672648.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/471e/7019209/8a454ab02dd8/ECAM2020-2672648.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/471e/7019209/4cdc095d315f/ECAM2020-2672648.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/471e/7019209/30677c0273f5/ECAM2020-2672648.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/471e/7019209/f1ab871daf0e/ECAM2020-2672648.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/471e/7019209/287a5659f671/ECAM2020-2672648.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/471e/7019209/8a454ab02dd8/ECAM2020-2672648.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/471e/7019209/4cdc095d315f/ECAM2020-2672648.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/471e/7019209/30677c0273f5/ECAM2020-2672648.005.jpg

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