mTOR/Survivin 信号通路在 TUA（2β, 3β, 23-三羟基熊果酸）诱导人胃癌 BGC823 细胞凋亡中的作用。
Involvement of mTOR/Survivin signaling pathway in TUA(2β, 3β, 23-trihydroxy-urs-12-ene-28-olic acid)-induced apoptosis in human gastric cancer cell line BGC823 cells.
机构信息
College of Pharmacy, Gannan Medical University, Ganzhou 341000, Jiangxi Province, PR China.
Department of Neurology, The Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine, Changsha 410006, Hunan Province, PR China.
出版信息
J Ethnopharmacol. 2021 Mar 1;267:113437. doi: 10.1016/j.jep.2020.113437. Epub 2020 Oct 1.
ETHNO-PHARMACOLOGICAL RELEVANCE: A natural ursolic compound, 2β,3β,23-trihydroxy-urs-12-ene-28-olic acid (TUA) was isolated from the root of Actinidiafulvicoma Hance. (A.fulvicoma Radix), which is used as a traditional hebal medicine to cure innominate inflammation of unknown origin of the digestive tract in the She nationality.
AIM OF THE STUDY
The aim of present study was to investigate the effects of TUA on gastric cancer and to clarify the potential mechanisms in human gastric cancer cell line BGC823 cells in vitro and in vivo.
MATERIALS AND METHODS
Cell proliferation, apoptosis, cell cycle, autophagy were all measured by MTS assay, flow cytometry following exposure to TUA. The mRNA expressions of PI3K, AKT, mTOR, P70S6K, Survivin and the protein expressions of p-PI3K, p-AKT, p-mTOR, p-P70S6K, Survivin were determined by qRT-PCR and Western blotting analysis, respectively. In vivo antitumor activity of TUA was assessed in a xenograft model.
RESULTS
In vitro studies showed that TUA significantly suppressed the viability of BGC823 cells in a concentration- and time-dependent manner but not GES-1 non-tumorigenic human gastric epithelial cells. TUA also significantly increased the apoptosis rate and the sub G2 population by cell cycle analysis in a concentration dependent manner. Exposure to TUA decreased PI3K, AKT, mTOR, P70S6K, Survivin mRNA, inhibited the phosphorylation of major receptors involved in autophagy and apoptosis, such as PI3K, AKT, mTOR and P70S6K, while reduced the expression of Survivin in BGC cells. In vivo studies showed that TUA decreased tumor volume and tumor weight and also down regulated the autophagy-related proteins expression.
CONCLUSIONS
TUA occupies underlying antitumor effects, the potential mechanisms may involve the suppression of mTOR/Survivin pathways connected to autophagy and the activation of apoptotic pathways in gastric cancer cells.
民族药理学相关性
从中华猕猴桃（A.fulvicoma Radix）的根部分离得到一种天然熊果酸化合物，2β,3β,23-三羟基-熊-12-烯-28-酸（TUA）。（A.fulvicoma Radix），用作治疗消化道无名炎症的传统草药，在 She 族。
研究目的
本研究旨在探讨 TUA 对胃癌的影响，并在体外和体内人胃癌 BGC823 细胞系中阐明其潜在机制。
材料和方法
采用 MTS 法检测 TUA 暴露后细胞增殖、凋亡、细胞周期、自噬的变化，采用 qRT-PCR 和 Western blot 分析分别检测 PI3K、AKT、mTOR、P70S6K、Survivin 的 mRNA 表达和 p-PI3K、p-AKT、p-mTOR、p-P70S6K、Survivin 的蛋白表达。采用异种移植模型评价 TUA 的体内抗肿瘤活性。
结果
体外研究表明，TUA 呈浓度和时间依赖性显著抑制 BGC823 细胞活力，但对非肿瘤性人类胃上皮细胞 GES-1 无影响。TUA 还显著增加了细胞周期分析中浓度依赖性的细胞凋亡率和亚 G2 群体。TUA 暴露后，PI3K、AKT、mTOR、P70S6K、Survivin mRNA 表达降低，抑制自噬和凋亡相关主要受体如 PI3K、AKT、mTOR 和 P70S6K 的磷酸化，同时降低 BGC 细胞中 Survivin 的表达。体内研究表明，TUA 可降低肿瘤体积和重量，下调自噬相关蛋白表达。
结论
TUA 具有抗肿瘤作用，其潜在机制可能涉及抑制与自噬相关的 mTOR/Survivin 通路和激活胃癌细胞中的凋亡通路。
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