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甘草酸通过诱导细胞周期阻滞和凋亡抑制胃癌细胞增殖。

Glycyrrhizic Acid Inhibits Proliferation of Gastric Cancer Cells by Inducing Cell Cycle Arrest and Apoptosis.

作者信息

Wang Hao, Ge Xuhui, Qu Huiheng, Wang Ning, Zhou Jiawen, Xu Wenjing, Xie Jingjing, Zhou Yongping, Shi Liqing, Qin Zhongke, Jiang Zhuang, Yin Wenjie, Xia Jiazeng

机构信息

Department of General Surgery and Translational Medicine Center, The Affiliated Wuxi No.2 People's Hospital of Nanjing Medical University, Wuxi 214002, Jiangsu, People's Republic of China.

Department of General Surgery, Wuxi Clinical College Affiliated to Nantong University, Wuxi 214002, Jiangsu, People's Republic of China.

出版信息

Cancer Manag Res. 2020 Apr 24;12:2853-2861. doi: 10.2147/CMAR.S244481. eCollection 2020.

Abstract

PURPOSE

Glycyrrhizic acid (GA) is the main active ingredient extracted from Chinese herb licorice root, and it shows anti-tumor effects in many cancer types, while its role in gastric cancer (GC) is still unknown. In this study, we evaluated the effects of GA on GC cells and explored the underlying mechanisms.

METHODS

The anti-proliferation effect of GA on GC cells was assessed by CCK-8, colony formation, and EdU assay. The effects of GA on cell cycle and apoptosis were detected by flow cytometer. Western blotting was performed to explore the underlying mechanisms.

RESULTS

Our results showed that GA had a time- and dose-dependent inhibitory effect on proliferation of GC cells. Flow cytometer analysis demonstrated that GA would lead to G1/S-phase arrest and apoptosis. GA treatment down-regulated the levels of G1 phase-related proteins, including cyclin D1, D2, D3, E1, and E2. In terms of apoptosis, GA treatment up-regulated the levels of Bax, cleaved PARP, and pro-caspase-3, -8, -9, but did not influence their cleavage patterns. The expression of Bcl-2, survivin and p65 was attenuated after treatment. Besides, GA would down-regulate the phosphorylation of PI3K/AKT pathway.

CONCLUSION

This study focused on inhibitory effect of GA on GC cells by inducing cell cycle arrest and apoptosis. Several important cyclins- and apoptosis-related proteins were involved in the regulation of GA to GC cells, and phosphorylated PI3K and AKT were attenuated. The results of this study indicated that GA is a potential and promising anti-cancer drug for GC.

摘要

目的

甘草酸(GA)是从中药甘草根中提取的主要活性成分,在多种癌症类型中显示出抗肿瘤作用,但其在胃癌(GC)中的作用仍不清楚。在本研究中,我们评估了GA对GC细胞的影响并探讨了潜在机制。

方法

通过CCK-8、集落形成和EdU测定评估GA对GC细胞的抗增殖作用。用流式细胞仪检测GA对细胞周期和凋亡的影响。进行蛋白质免疫印迹法以探索潜在机制。

结果

我们的结果表明,GA对GC细胞的增殖具有时间和剂量依赖性抑制作用。流式细胞仪分析表明,GA会导致G1/S期阻滞和凋亡。GA处理下调了G1期相关蛋白的水平,包括细胞周期蛋白D1、D2、D3、E1和E2。在凋亡方面,GA处理上调了Bax、裂解的PARP以及前半胱天冬酶-3、-8、-9的水平,但不影响它们的裂解模式。处理后Bcl-2、生存素和p65的表达减弱。此外,GA会下调PI3K/AKT通路的磷酸化。

结论

本研究聚焦于GA通过诱导细胞周期阻滞和凋亡对GC细胞的抑制作用。几种重要的细胞周期蛋白和凋亡相关蛋白参与了GA对GC细胞的调节,并且磷酸化的PI3K和AKT减弱。本研究结果表明,GA是一种对GC有潜力且有前景的抗癌药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/414c/7187946/6fcb3818f15f/CMAR-12-2853-g0001.jpg

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