Naringin induces apoptosis of gastric carcinoma cells via blocking the PI3K/AKT pathway and activating pro-death autophagy

被引:24
作者
Xu, Cuixiang [1 ]
Huang, Xiaoyan [1 ]
Huang, Yubin [2 ,3 ]
Liu, Xiao [2 ,3 ]
Wu, Min [4 ]
Wang, Jianhua [3 ]
Duan, Xianglong [3 ,5 ,6 ]
机构
[1] Shaanxi Prov Peoples Hosp, Shaanxi Prov Key Lab Infect & Immune Dis, Xian 710068, Shaanxi, Peoples R China
[2] Xian Med Univ, Clin Dept, Xian 710021, Shaanxi, Peoples R China
[3] Shaanxi Prov Peoples Hosp, Dept Gen Surg 2, 256 Youyi West Rd, Xian 710068, Shaanxi, Peoples R China
[4] Shaanxi Prov Peoples Hosp, Dept Res, Xian 710068, Shaanxi, Peoples R China
[5] Northwestern Polytech Univ, Affiliated Hosp, Dept Gen Surg, Xian 710072, Shaanxi, Peoples R China
[6] Tibet Nationalities Univ, Clin Dept, Xianyang 712082, Shaanxi, Peoples R China
基金
中国国家自然科学基金;
关键词
apoptosis; cell autophagy; gastric carcinoma SNU-1 cells; naringin; PI3K; AKT; MEDIATED APOPTOSIS; CYCLE ARREST; CANCER; FLAVONOIDS; GROWTH; INHIBITION; MECHANISMS; STRESS; DEATH; MICE;
D O I
10.3892/mmr.2021.12412
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Naringin (Nar) is one of the natural glycosides extracted from pomelo and other citrus fruits. It has various pharmacological activities, including anti-inflammatory, antioxidant, anti-proliferative and anti-cancer. However, the underlying mechanisms by which Nar regulates apoptosis and autophagy in gastric cancer remain unclear. Thus, the present study aimed to assess the therapeutic effect of Nar and the underlying mechanisms. SNU-1 cell proliferation was determined using Cell Counting Kit-8 assay. Cell morphological changes were observed under a phase-contrast microscope. The changes in the cell cycle were determined using flow cytometry analysis and the changes in cell apoptosis were determined using flow cytometry, Hoechst 33258 and TUNEL staining. The protein levels pertaining to the PI3K/AKT pathway and cell apoptosis and autophagy were monitored using western blot analysis. The results demonstrated that Nar significantly inhibited SNU-1 cell growth and induced cell cycle arrest in the G(0)/G(1) phase and cell apoptosis. Further mechanistic studies demonstrated that Nar blocked the PI3K/AKT pathway, activated cell autophagy and stimulated the expression of apoptosis-associated protein cleaved caspase 3 and Bax, but decreased the expression of Bcl-2. Preincubating SNU-1 cells with 3-methyladenine, a cell-autophagy inhibitor, significantly alleviated the effects of Nar in promoting cell apoptosis and cleaved caspase 3 expression. It was concluded that Nar promoted SNU-1 cell apoptosis via blocking the PI3K/AKT signaling pathway and activating cell autophagy.
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页数:10
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